11,912 results match your criteria Human Genetics [Journal]


Correction to: Gene therapies in canine models for Duchenne muscular dystrophy.

Hum Genet 2019 Feb 19. Epub 2019 Feb 19.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX, 77843-4458, USA.

The authors would like to correct the following information concerning Conflict of Interest. Read More

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http://dx.doi.org/10.1007/s00439-019-01982-1DOI Listing
February 2019

PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly.

Hum Genet 2019 Feb 18. Epub 2019 Feb 18.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Pseudouridylation is the most common post-transcriptional modification, wherein uridine is isomerized into 5-ribosyluracil (pseudouridine, Ψ). The resulting increase in base stacking and creation of additional hydrogen bonds are thought to enhance RNA stability. Pseudouridine synthases are encoded in humans by 13 genes, two of which are linked to Mendelian diseases: PUS1 and PUS3. Read More

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http://dx.doi.org/10.1007/s00439-019-01980-3DOI Listing
February 2019

Gene panel sequencing identifies a likely monogenic cause in 7% of 235 Pakistani families with nephrolithiasis.

Hum Genet 2019 Feb 18. Epub 2019 Feb 18.

Division of Nephrology, Department of Medicine, Harvard Medical School, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.

Nephrolithiasis (NL) affects 1 in 11 individuals worldwide and causes significant patient morbidity. We previously demonstrated a genetic cause of NL can be identified in 11-29% of pre-dominantly American and European stone formers. Pakistan, which resides within the Afro-Asian stone belt, has a high prevalence of nephrolithiasis (12%) as well as high rate of consanguinity (> 50%). Read More

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http://dx.doi.org/10.1007/s00439-019-01978-xDOI Listing
February 2019

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia.

Hum Genet 2019 Feb 14. Epub 2019 Feb 14.

Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.

Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Read More

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http://dx.doi.org/10.1007/s00439-019-01977-yDOI Listing
February 2019

NUP214 deficiency causes severe encephalopathy and microcephaly in humans.

Hum Genet 2019 Feb 13. Epub 2019 Feb 13.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Nuclear pore complex (NPC) is a fundamental component of the nuclear envelope and is key to the nucleocytoplasmic transport. Mutations in several NUP genes that encode individual components of NPC known as nucleoporins have been identified in recent years among patients with static encephalopathies characterized by developmental delay and microcephaly. We describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death. Read More

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http://dx.doi.org/10.1007/s00439-019-01979-wDOI Listing
February 2019

Gene therapies in canine models for Duchenne muscular dystrophy.

Hum Genet 2019 Feb 7. Epub 2019 Feb 7.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX, 77843-4458, USA.

Therapies for Duchenne muscular dystrophy (DMD) must first be tested in animal models to determine proof-of-concept, efficacy, and importantly, safety. The murine and canine models for DMD are genetically homologous and most commonly used in pre-clinical testing. Although the mouse is a strong, proof-of-concept model, affected dogs show more analogous clinical and immunological disease progression compared to boys with DMD. Read More

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http://dx.doi.org/10.1007/s00439-019-01976-zDOI Listing
February 2019

A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death.

Hum Genet 2019 Feb 4. Epub 2019 Feb 4.

Department of Physiology, University of Arizona, Tucson, AZ, 85724, USA.

The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. Read More

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http://dx.doi.org/10.1007/s00439-019-01973-2DOI Listing
February 2019
2 Reads

Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus.

Hum Genet 2019 Feb 1;138(2):141-150. Epub 2019 Feb 1.

Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 23, Uppsala, Sweden.

Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Read More

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http://link.springer.com/10.1007/s00439-018-01966-7
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http://dx.doi.org/10.1007/s00439-018-01966-7DOI Listing
February 2019
3 Reads

Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.

Hum Genet 2019 Feb 22;138(2):199-210. Epub 2019 Jan 22.

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0. Read More

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http://dx.doi.org/10.1007/s00439-019-01975-0DOI Listing
February 2019
1 Read

Translating cancer genomics into precision medicine with artificial intelligence: applications, challenges and future perspectives.

Hum Genet 2019 Feb 22;138(2):109-124. Epub 2019 Jan 22.

IBM Watson Health, Cambridge, MA, USA.

In the field of cancer genomics, the broad availability of genetic information offered by next-generation sequencing technologies and rapid growth in biomedical publication has led to the advent of the big-data era. Integration of artificial intelligence (AI) approaches such as machine learning, deep learning, and natural language processing (NLP) to tackle the challenges of scalability and high dimensionality of data and to transform big data into clinically actionable knowledge is expanding and becoming the foundation of precision medicine. In this paper, we review the current status and future directions of AI application in cancer genomics within the context of workflows to integrate genomic analysis for precision cancer care. Read More

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http://dx.doi.org/10.1007/s00439-019-01970-5DOI Listing
February 2019

LncRNA ZBTB40-IT1 modulated by osteoporosis GWAS risk SNPs suppresses osteogenesis.

Hum Genet 2019 Feb 19;138(2):151-166. Epub 2019 Jan 19.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China.

Previous genome-wide linkage and association studies have identified an osteoporosis-associated locus at 1p36 that harbors SNPs rs34920465 and rs6426749. The 1p36 locus also comprises the WNT4 gene with known role in bone metabolism and functionally unknown ZBTB40/lncRNA ZBTB40-IT1 genes. How these might interact to contribute to osteoporosis susceptibility is not known. Read More

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http://dx.doi.org/10.1007/s00439-019-01969-yDOI Listing
February 2019
5 Reads

Integrative genomic analysis predicts novel functional enhancer-SNPs for bone mineral density.

Hum Genet 2019 Feb 17;138(2):167-185. Epub 2019 Jan 17.

Department of Global Biostatistics and Data Science, Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1601, New Orleans, LA, 70112, USA.

Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD) and deterioration of bone microarchitecture. To identify novel genetic loci underlying osteoporosis, an effective strategy is to focus on scanning of variants with high potential functional impacts. Enhancers play a crucial role in regulating cell-type-specific transcription. Read More

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http://dx.doi.org/10.1007/s00439-019-01971-4DOI Listing
February 2019
1 Read

Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epileptic encephalopathy with brain hypomyelination and cerebellar atrophy.

Hum Genet 2019 Feb 17;138(2):187-198. Epub 2019 Jan 17.

Oasi Research Institute-IRCCS, Troina, Italy.

Developmental and epileptic encephalopathies (DEEs) are genetically heterogenous conditions, often characterized by early onset, EEG interictal epileptiform abnormalities, polymorphous and drug-resistant seizures, and neurodevelopmental impairments. In this study, we investigated the genetic defects in two siblings who presented with severe DEE, microcephaly, spastic tetraplegia, diffuse brain hypomyelination, cerebellar atrophy, short stature, and kyphoscoliosis. Whole exome next-generation sequencing (WES) identified in both siblings a homozygous non-sense variant in the ACTL6B gene (NM_016188:c. Read More

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http://dx.doi.org/10.1007/s00439-019-01972-3DOI Listing
February 2019

New insights into the genetics of spermatogenic failure: a review of the literature.

Hum Genet 2019 Feb 17;138(2):125-140. Epub 2019 Jan 17.

Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", via S. Sofia 78, 95123, Catania, Italy.

Genetic anomalies are known to affect about 15% of infertile patients with azoospermia or severe oligozoospermia. Despite a throughout diagnostic work-up, in up to the 72% of the male partners of infertile couples, no etiological factor can be found; hence, the cause of infertility remains unclear. Recently, several novel genetic causes of spermatogenic failure (SPGF) have been described. Read More

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http://dx.doi.org/10.1007/s00439-019-01974-1DOI Listing
February 2019
4.824 Impact Factor

Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome.

Hum Genet 2019 Jan 9;138(1):93-103. Epub 2019 Jan 9.

Genetics Division, Universidade Federal de São Paulo, São Paulo, Brazil.

The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromosome 22q11. Read More

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http://link.springer.com/10.1007/s00439-018-01967-6
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http://dx.doi.org/10.1007/s00439-018-01967-6DOI Listing
January 2019
6 Reads

Prospects and modalities for the treatment of genetic ocular anomalies.

Hum Genet 2019 Jan 2. Epub 2019 Jan 2.

Department of Ophthalmology and Visual Sciences, University of British Columbia, 2550 Willow Street, Vancouver, BC, V5Z 3N9, Canada.

Over the last three decades, genetic studies have made great strides toward the identification of genes and genetic mechanisms underlying congenital disorders of the eye. However, despite the vast knowledge available this has not translated into treatments to prevent or repair the damage in the clinical setting. Recently, new research in technologies, such as tissue regeneration, next generation designer drugs, and genome editing, have become available for some genetic disorders that might be applicable to congenital ocular diseases in the near future. Read More

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http://link.springer.com/10.1007/s00439-018-01968-5
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http://dx.doi.org/10.1007/s00439-018-01968-5DOI Listing
January 2019
3 Reads

Whole-exome sequencing reveals SALL4 variants in premature ovarian insufficiency: an update on genotype-phenotype correlations.

Hum Genet 2019 Jan 2;138(1):83-92. Epub 2019 Jan 2.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Life Sciences, Fudan University, Shanghai, 200011, China.

Premature ovarian insufficiency (POI) is a severe female disorder characterized by primary or secondary amenorrhea before 40 years of age. Genetic factors have been implicated in the pathogenesis of POI, but known POI-associated genes account for only a small fraction of heritability. Here, we performed whole-exome sequencing (WES) to explore pathogenic genes in Han Chinese subjects with POI. Read More

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http://dx.doi.org/10.1007/s00439-018-1962-4DOI Listing
January 2019
2 Reads

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans.

Hum Genet 2019 Jan 10;138(1):49-60. Epub 2018 Dec 10.

Department of Public Health Sciences, University of Chicago, Chicago, IL, 60615, USA.

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i. Read More

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http://link.springer.com/10.1007/s00439-018-1964-2
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http://dx.doi.org/10.1007/s00439-018-1964-2DOI Listing
January 2019
8 Reads
4.824 Impact Factor

De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.

Hum Genet 2019 Jan 8;138(1):61-72. Epub 2018 Dec 8.

Hearing and Genes, Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.

ATP2B2 encodes the PMCA2 Ca pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans. Read More

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http://link.springer.com/10.1007/s00439-018-1965-1
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http://dx.doi.org/10.1007/s00439-018-1965-1DOI Listing
January 2019
7 Reads

A novel ISLR2-linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension.

Hum Genet 2019 Jan 27;138(1):105-107. Epub 2018 Nov 27.

Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

ISLR2 (immunoglobulin superfamily containing leucine-rich repeat 2), encodes a protein involved in axon guidance in brain development (hence the other name leucine-rich repeat domain- and immunoglobulin domain-containing axon extension proteins; LINX). A recently described mouse knockout displays hydrocephalus. However, the corresponding phenotype in humans is unknown. Read More

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http://dx.doi.org/10.1007/s00439-018-1963-3DOI Listing
January 2019

Ultra-deep amplicon sequencing indicates absence of low-grade mosaicism with normal cells in patients with type-1 NF1 deletions.

Hum Genet 2019 Jan 26;138(1):73-81. Epub 2018 Nov 26.

Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

Different types of large NF1 deletion are distinguishable by breakpoint location and potentially also by the frequency of mosaicism with normal cells lacking the deletion. However, low-grade mosaicism with fewer than 10% normal cells has not yet been excluded for all NF1 deletion types since it is impossible to assess by the standard techniques used to identify such deletions, including MLPA and array analysis. Here, we used ultra-deep amplicon sequencing to investigate the presence of normal cells in the blood of 20 patients with type-1 NF1 deletions lacking mosaicism according to MLPA. Read More

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http://dx.doi.org/10.1007/s00439-018-1961-5DOI Listing
January 2019
1 Read

Complement component 4 variations may influence psychopathology risk in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Hum Genet 2018 Dec 21;137(11-12):955-960. Epub 2018 Nov 21.

National Institutes of Health Clinical Center, 10 Center Drive, Room 1-2740, Bethesda, MD, 20892-1932, USA.

CYP21A2 defects result in congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by impaired adrenal steroidogenesis. CYP21A2 lies within the major histocompatibility complex in an area of the genome highly susceptible to genetic variation. Alterations in the neighboring complement component 4 isotypes C4A and C4B have been associated with psychiatric and autoimmune disease. Read More

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http://link.springer.com/10.1007/s00439-018-1959-z
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http://dx.doi.org/10.1007/s00439-018-1959-zDOI Listing
December 2018
13 Reads

SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy.

Hum Genet 2018 Dec 21;137(11-12):911-919. Epub 2018 Nov 21.

Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany.

Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state. Read More

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http://dx.doi.org/10.1007/s00439-018-1952-6DOI Listing
December 2018
3 Reads

Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.

Hum Genet 2018 Dec 19;137(11-12):921-939. Epub 2018 Nov 19.

Warren Alpert Medical School of Brown University, Providence, RI, USA.

Juvenile segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ starting in childhood. Hutchinson-Gilford progeria syndrome (HGPS), caused by a recurrent de novo synonymous LMNA mutation resulting in aberrant splicing and generation of a mutant product called progerin, is a prototypical example of such disorders. Here, we performed a joint collaborative study using massively parallel sequencing and targeted Sanger sequencing, aimed at delineating the underlying genetic cause of 14 previously undiagnosed, clinically heterogeneous, non-LMNA-associated juvenile progeroid patients. Read More

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http://dx.doi.org/10.1007/s00439-018-1957-1DOI Listing
December 2018
6 Reads
4.824 Impact Factor

Chromosome 18 gene dosage map 2.0.

Hum Genet 2018 Dec 17;137(11-12):961-970. Epub 2018 Nov 17.

Department of Pediatrics, The Chromosome 18 Clinical Research Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.

In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. Read More

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http://link.springer.com/10.1007/s00439-018-1960-6
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http://dx.doi.org/10.1007/s00439-018-1960-6DOI Listing
December 2018
11 Reads

Standards and guidelines for canine clinical genetic testing laboratories.

Hum Genet 2018 Nov 13. Epub 2018 Nov 13.

Paw Print Genetics, Genetic Veterinary Sciences, Inc., 220 E Rowan, Suite 220, Spokane, WA, 99207, USA.

This publication represents a proposed approach to quality standards and guidelines for canine clinical genetic testing laboratories. Currently, there are no guidelines for laboratories performing clinical testing on dogs. Thus, there is no consensus set of protocols that set the minimal standards of quality among these laboratories, potentially causing variable results between laboratories, inconsistencies in reporting, and the inability to share information that could impact testing among organizations. Read More

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http://link.springer.com/10.1007/s00439-018-1954-4
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http://dx.doi.org/10.1007/s00439-018-1954-4DOI Listing
November 2018
1 Read

RNA sequencing-based transcriptomic profiles of embryonic lens development for cataract gene discovery.

Hum Genet 2018 Dec 11;137(11-12):941-954. Epub 2018 Nov 11.

Department of Biological Sciences, University of Delaware, 105 The Green, Delaware Avenue, 236 Wolf Hall, Newark, DE, 19716, USA.

Isolated or syndromic congenital cataracts are heterogeneous developmental defects, making the identification of the associated genes challenging. In the past, mouse lens expression microarrays have been successfully applied in bioinformatics tools (e.g. Read More

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http://dx.doi.org/10.1007/s00439-018-1958-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342005PMC
December 2018

Genetic association and differential expression of PITX2 with acute appendicitis.

Hum Genet 2019 Jan 3;138(1):37-47. Epub 2018 Nov 3.

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

Appendicitis affects 9% of Americans and is the most common diagnosis requiring hospitalization of both children and adults. We performed a genome-wide association study of self-reported appendectomy with 18,773 affected adults and 114,907 unaffected adults of European American ancestry. A significant association with appendectomy was observed at 4q25 near the gene PITX2 (rs2129979, p value = 8. Read More

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http://dx.doi.org/10.1007/s00439-018-1956-2DOI Listing
January 2019
2 Reads

Ways of improving precise knock-in by genome-editing technologies.

Hum Genet 2019 Jan 2;138(1):1-19. Epub 2018 Nov 2.

Laboratory of Mutagenesis, Federal State Budgetary Institution "Research Centre for Medical Genetics", Moskvorechie, 1, Moscow, 115522, Russia.

Despite the recent discover of genome-editing methods, today we can say these approaches have firmly entered our life. Two approaches-knocking out malfunctioning gene allele or correcting the mutation with precise knock-in-can be used in hereditary monogenic diseases treatment. The latter approach is relatively ineffective. Read More

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http://dx.doi.org/10.1007/s00439-018-1953-5DOI Listing
January 2019

The RNA world of human ageing.

Hum Genet 2018 Dec 1;137(11-12):865-879. Epub 2018 Nov 1.

Dirección de Investigación, Instituto Nacional de Geriatría (INGER), Blvd. Adolfo Ruiz Cortines 2767, 10200, Mexico City, Mexico.

Ageing is one of the most complex processes in nature; how could we prevent the associated biological changes and chronic diseases that string along with this process, is a challenge in healthcare around the world. Recent advances in next-generation sequencing have reached a stage where it is possible to know from a specific tissue the most abundant transcripts, alternative splicing process and, non-coding RNA molecules (microRNA's, long non-coding RNA's, and circular RNAs). Moreover, our knowledge of several biological processes related to ageing such as senescence and autophagy have dramatically increased in the last years. Read More

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http://link.springer.com/10.1007/s00439-018-1955-3
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http://dx.doi.org/10.1007/s00439-018-1955-3DOI Listing
December 2018
1 Read

Human eye conditions: insights from the fly eye.

Hum Genet 2018 Nov 1. Epub 2018 Nov 1.

Department of Biological and Medical Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.

The fruit fly Drosophila melanogaster has served as an excellent model to study and understand the genetics of many human diseases from cancer to neurodegeneration. Studying the regulation of growth, determination and differentiation of the compound eyes of this fly, in particular, have provided key insights into a wide range of diseases. Here we review the regulation of the development of fly eyes in light of shared aspects with human eye development. Read More

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http://link.springer.com/10.1007/s00439-018-1948-2
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http://dx.doi.org/10.1007/s00439-018-1948-2DOI Listing
November 2018
1 Read

Genetics of anophthalmia and microphthalmia. Part 2: Syndromes associated with anophthalmia-microphthalmia.

Authors:
Anne Slavotinek

Hum Genet 2018 Oct 30. Epub 2018 Oct 30.

Division of Genetics, Department of Pediatrics, University of California, San Francisco Room RH384C, 1550 4th St, San Francisco, CA, 94143-2711, USA.

As new genes for A/M are identified in the genomic era, the number of syndromes associated with A/M has greatly expanded. In this review, we provide a brief synopsis of the clinical presentation and molecular genetic etiology of previously characterized pathways involved in A/M, including the Sex-determining region Y-box 2 (SOX2), Orthodenticle Homeobox 2 (OTX2) and Paired box protein-6 (PAX6) genes, and the Stimulated by retinoic acid gene 6 homolog (STRA6), Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3), and RA Receptor Beta (RARβ) genes that are involved in retinoic acid synthesis. Less common genetic causes of A/M, including genes involved in BMP signaling [Bone Morphogenetic Protein 4 (BMP4), Bone Morphogenetic Protein 7 (BMP7) and SPARC-related modular calcium-binding protein 1 (SMOC1)], genes involved in the mitochondrial respiratory chain complex [Holocytochrome c-type synthase (HCCS), Cytochrome C Oxidase Subunit 7B (COX7B), and NADH:Ubiquinone Oxidoreductase subunit B11 (NDUFB11)], the BCL-6 corepressor gene (BCOR), Yes-Associated Protein 1 (YAP1) and Transcription Factor AP-2 Alpha (TFAP2α), are more briefly discussed. Read More

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http://link.springer.com/10.1007/s00439-018-1949-1
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http://dx.doi.org/10.1007/s00439-018-1949-1DOI Listing
October 2018
9 Reads

Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes.

Hum Genet 2019 Jan 27;138(1):21-35. Epub 2018 Oct 27.

Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan.

RASopathies are a group of developmental disorders caused by mutations in genes that regulate the RAS/MAPK pathway and include Noonan syndrome (NS), Costello syndrome, cardiofaciocutaneous syndrome and other related disorders. Whole exome sequencing studies recently identified LZTR1, PPP1CB and MRAS as new causative genes in RASopathies. However, information on the phenotypes of LZTR1 mutation-positive patients and functional properties of the mutations are limited. Read More

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http://dx.doi.org/10.1007/s00439-018-1951-7DOI Listing
January 2019
10 Reads

Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype.

Hum Genet 2018 Dec 27;137(11-12):905-909. Epub 2018 Oct 27.

Divisions of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada.

Lowry-Wood syndrome (LWS) is a skeletal dysplasia characterized by multiple epiphyseal dysplasia associated with microcephaly, developmental delay and intellectual disability, and eye involvement. Pathogenic variants in RNU4ATAC, an RNA of the minor spliceosome important for the excision of U12-dependent introns, have been recently associated with LWS. This gene had previously also been associated with microcephalic osteodysplastic primordial dwarfism (MOPD) and Roifman syndrome (RS), two distinct conditions which share with LWS some skeletal and neurological anomalies. Read More

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http://link.springer.com/10.1007/s00439-018-1950-8
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http://dx.doi.org/10.1007/s00439-018-1950-8DOI Listing
December 2018
9 Reads
4.824 Impact Factor

The impact of GJA8 SNPs on susceptibility to age-related cataract.

Hum Genet 2018 Dec 22;137(11-12):897-904. Epub 2018 Oct 22.

Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. Read More

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http://link.springer.com/10.1007/s00439-018-1945-5
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http://dx.doi.org/10.1007/s00439-018-1945-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267713PMC
December 2018
6 Reads

Personalised medicine and population health: breast and ovarian cancer.

Authors:
Steven A Narod

Hum Genet 2018 Oct 17;137(10):769-778. Epub 2018 Oct 17.

Women's College Research Institute, Women's College Hospital, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada.

It has been suggested that a personalised approach to cancer prevention and screening might lead to a new paradigm for cancer control. Various aspects include testing for high-penetrance cancer susceptibility genes and generating personal risks scores, based on panels of single nucleotide polymorphisms. These tests can categorize women into various groupings of risk for cancer prevention (surgery and chemoprevention) cancer screening and prevention of cancer recurrence. Read More

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http://link.springer.com/10.1007/s00439-018-1944-6
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http://dx.doi.org/10.1007/s00439-018-1944-6DOI Listing
October 2018
14 Reads

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Hum Genet 2018 Oct 13;137(10):847-862. Epub 2018 Oct 13.

Department of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. Read More

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http://dx.doi.org/10.1007/s00439-018-1943-7DOI Listing
October 2018
6 Reads

Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.

Hum Genet 2018 Dec 10;137(11-12):881-896. Epub 2018 Oct 10.

School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, UK.

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Read More

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http://dx.doi.org/10.1007/s00439-018-1942-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267700PMC
December 2018

Implication of non-coding PAX6 mutations in aniridia.

Hum Genet 2018 Oct 5;137(10):831-846. Epub 2018 Oct 5.

Department of Genetics, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz University Hospital-Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.

There is an increasing implication of non-coding regions in pathological processes of genetic origin. This is partly due to the emergence of sophisticated techniques that have transformed research into gene expression by allowing a more global understanding of the genome, both at the genomic, epigenomic and chromatin levels. Here, we implemented the analysis of PAX6, whose coding loss-of-function variants are mainly implied in aniridia, by studying its non-coding regions (untranslated regions, introns and cis-regulatory sequences). Read More

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http://link.springer.com/10.1007/s00439-018-1940-x
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http://dx.doi.org/10.1007/s00439-018-1940-xDOI Listing
October 2018
3 Reads

De novo unbalanced translocations have a complex history/aetiology.

Hum Genet 2018 Oct 1;137(10):817-829. Epub 2018 Oct 1.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was detected in 6 cases, whereas in 46, both imbalances have the same parental origin. Read More

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http://dx.doi.org/10.1007/s00439-018-1941-9DOI Listing
October 2018
17 Reads

Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder.

Hum Genet 2018 Oct 1;137(10):807-815. Epub 2018 Oct 1.

Division of Medical Genetics, Department of Medicine, University of Washington, Box 359460, Seattle, WA, 98195, USA.

Hundreds of genes have been implicated in autism spectrum disorders (ASDs). In genetically heterogeneous conditions, large families with multiple affected individuals provide strong evidence implicating a rare variant, and replication of the same variant in multiple families is unusual. We previously published linkage analyses and follow-up exome sequencing in seven large families with ASDs, implicating 14 rare exome variants. Read More

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http://link.springer.com/10.1007/s00439-018-1939-3
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http://dx.doi.org/10.1007/s00439-018-1939-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309233PMC
October 2018
2 Reads

Rare loss of function variants in candidate genes and risk of colorectal cancer.

Hum Genet 2018 Oct 28;137(10):795-806. Epub 2018 Sep 28.

Division of Medical Genetics, School of Medicine, University of Washington Medical Center, Seattle, WA, USA.

Although ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. Read More

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http://dx.doi.org/10.1007/s00439-018-1938-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283057PMC
October 2018
13 Reads

The genetic architecture of aniridia and Gillespie syndrome.

Hum Genet 2018 Sep 22. Epub 2018 Sep 22.

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.

Absence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygous PAX6 loss-of-function mutations. Read More

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http://dx.doi.org/10.1007/s00439-018-1934-8DOI Listing
September 2018
1 Read

Knockout of ush2a gene in zebrafish causes hearing impairment and late onset rod-cone dystrophy.

Hum Genet 2018 Oct 21;137(10):779-794. Epub 2018 Sep 21.

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Rd., Wuhan, 430074, Hubei, People's Republic of China.

Most cases of Usher syndrome type II (USH2) are due to mutations in the USH2A gene. There are no effective treatments or ideal animal models for this disease, and the pathological mechanisms of USH2 caused by USH2A mutations are still unknown. Here, we constructed a ush2a knockout (ush2a) zebrafish model using TALEN technology to investigate the molecular pathology of USH2. Read More

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http://dx.doi.org/10.1007/s00439-018-1936-6DOI Listing
October 2018
17 Reads
4.824 Impact Factor

Phenotype-genotype correlations and emerging pathways in ocular anterior segment dysgenesis.

Hum Genet 2018 Sep 21. Epub 2018 Sep 21.

Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, The University of Sydney, Sydney, NSW, 2145, Australia.

Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, as well as syndromal associations. These conditions have a significant impact on vision due to disruption of the visual axis, and also secondary glaucoma which occurs in over 50% of patients. Ocular anterior segment disorders occur due to a complex interplay of developmental, embryological and genetic factors, and often have phenotypic overlaps and genetic heterogeneity. Read More

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http://dx.doi.org/10.1007/s00439-018-1935-7DOI Listing
September 2018

Correction to: The study of human Y chromosome variation through ancient DNA.

Authors:
Toomas Kivisild

Hum Genet 2018 Oct;137(10):863

Department of Archaeology and Anthropology, University of Cambridge, Cambridge, CB2 1QH, UK.

The following sentence on the 11th page of the article. Read More

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http://dx.doi.org/10.1007/s00439-018-1937-5DOI Listing
October 2018
5 Reads

Application of CRISPR/Cas9 technologies combined with iPSCs in the study and treatment of retinal degenerative diseases.

Hum Genet 2018 Sep 10;137(9):679-688. Epub 2018 Sep 10.

Tianjin Medical University Eye Hospital, Tianjin, 300384, China.

Retinal degeneration diseases, such as age-related macular degeneration and retinitis pigmentosa, affect millions of people worldwide and are major causes of irreversible blindness. Effective treatments for retinal degeneration, including drug therapy, gene augmentation or transplantation approaches, have been widely investigated. Nevertheless, more research should be dedicated to therapeutic methods to improve future clinical treatments. Read More

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http://link.springer.com/10.1007/s00439-018-1933-9
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http://dx.doi.org/10.1007/s00439-018-1933-9DOI Listing
September 2018
6 Reads
4.824 Impact Factor

Genetic landscape of isolated pediatric cataracts: extreme heterogeneity and variable inheritance patterns within genes.

Hum Genet 2018 Sep 5. Epub 2018 Sep 5.

Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.

Pediatric cataract represents an important cause of pediatric visual impairment. While both genetic and environmental causes for pediatric cataract are known, a large proportion remains idiopathic. The purpose of this review is to discuss genes involved in isolated pediatric cataract, with a focus on variable inheritance patterns within genes. Read More

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http://dx.doi.org/10.1007/s00439-018-1932-xDOI Listing
September 2018

Non-coding RNAs in retinal development and function.

Hum Genet 2018 Sep 5. Epub 2018 Sep 5.

Medical Genetics, Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Via Luigi De Crecchio 7, 80138, Naples, Italy.

Accumulating evidence on the role of non-protein-coding RNA sequences in the regulation of gene expression is greatly expanding our understanding of the flow of genetic information within biological systems. The interplay between protein-coding and non-coding RNAs (ncRNAs) is essential for tissue development, homeostasis, and function. NcRNAs can be divided in short ncRNAs, whose main subtype is represented by microRNAs, and long ncRNAs, which constitute a more heterogeneous class. Read More

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http://dx.doi.org/10.1007/s00439-018-1931-yDOI Listing
September 2018
13 Reads

Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies).

Hum Genet 2018 Sep 23;137(9):753-768. Epub 2018 Aug 23.

Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.

NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. Read More

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http://dx.doi.org/10.1007/s00439-018-1929-5DOI Listing
September 2018
7 Reads
4.824 Impact Factor