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    7557 results match your criteria Clinical Genetics [Journal]

    1 OF 152

    Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.
    Clin Genet 2017 Sep 19. Epub 2017 Sep 19.
    Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
    Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous etiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Read More

    Management of Leigh Syndrome: current status and new insights.
    Clin Genet 2017 Sep 14. Epub 2017 Sep 14.
    Department of Medicine, the University of Hong Kong, Hong Kong SAR, P. R. China.
    Leigh syndrome (LS) is an inherited mitochondrial encephalopathy associated with gene mutations of oxidative phosphorylation(OXPHOS) pathway that result in early disability and death in affected young children. Currently, LS is incurable and unresponsive to many treatments, although some case reports indicate that supplements can improve the condition. Many novel therapies are being continuously tested in preclinical studies. Read More

    TSGA10 is a novel candidate gene associated with acephalic spermatozoa.
    Clin Genet 2017 Sep 14. Epub 2017 Sep 14.
    Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing, 100026, China.
    Acephalic spermatozoa is a rare teratozoospermia associated with male infertility. However, the pathogenesis of this disorder remains unclear. Here, we report a 27-year-old infertile male from a consanguineous family, who presented with 99% headless sperm in his ejaculate. Read More

    Genetic and Epigenetic Insights into Uveal Melanoma.
    Clin Genet 2017 Sep 13. Epub 2017 Sep 13.
    Department of Ophthalmology, University of Bonn, Germany.
    Uveal melanoma (UM) is the most frequent primary intraocular tumor in Caucasian adults and is potentially fatal if metastases develop. While several prognostic genetic changes have been identified in UM, epigenetic influences are now getting closer attention. Recent technological advances have allowed to examine the human genome to a greater extent and have improved our understanding of several diseases including malignant tumors. Read More

    Expanding the clinical and molecular spectrum of PRMT7 mutations: three additional patients and review.
    Clin Genet 2017 Sep 13. Epub 2017 Sep 13.
    Laboratory of Medical Genetics, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
    Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, seven patients have been described harboring compound heterozygous or homozygous variants in the PRMT7 gene, causing a novel intellectual disability syndrome, known as SBIDDS syndrome (Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures). Read More

    mTOR mutations in Smith-Kingsmore syndrome: four additional patients and a review.
    Clin Genet 2017 Sep 11. Epub 2017 Sep 11.
    CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, 28029, Madrid, Spain.
    Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA: 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Read More

    Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation.
    Clin Genet 2017 Sep 11. Epub 2017 Sep 11.
    UOC Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
    Beukes Hip Dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c. Read More

    Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance.
    Clin Genet 2017 Sep 7. Epub 2017 Sep 7.
    Ambry Genetics, Division of Clinical Genomics, Aliso Viejo, CA, USA.
    Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SETD5 phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Read More

    Diagnostic exome sequencing in early-onset Parkinson's disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson's disease.
    Clin Genet 2017 Sep 1. Epub 2017 Sep 1.
    Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
    Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole exome sequencing could be an efficient approach to genetic testing in PD. To evaluate its performance in early-onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD. Read More

    Recessive Mutations in NDUFA2 Cause Mitochondrial Leukoencephalopathy.
    Clin Genet 2017 Aug 30. Epub 2017 Aug 30.
    Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
    Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report two patients with cystic leukoencephalopathy and complex I deficiency with recessive mutations in NDUFA2, an accessory subunit of complex I. The first patient was initially diagnosed with a primary systemic carnitine deficiency associated with a homozygous variant in SLC22A5, but also exhibited developmental regression and cystic leukoencephalopathy, and an additional diagnosis of complex I deficiency was suspected. Read More

    Development and validation of a severity scoring system for Zellweger spectrum disorders.
    Clin Genet 2017 Aug 30. Epub 2017 Aug 30.
    Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
    The lack of a validated severity scoring system for individuals with Zellweger spectrum disorders (ZSD) hampers optimal patient care and reliable research. Here, we describe the development of such severity score and its validation in a large, well characterized cohort of ZSD individuals. We developed a severity scoring system based on the 14 organs that typically can be affected in ZSD. Read More

    Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: lumping or splitting?
    Clin Genet 2017 Aug 30. Epub 2017 Aug 30.
    Medical Genetics Unit, A.O.R.N. "G. Rummo", Benevento, Italy.
    The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are two rare but clinically well-described diseases caused by de novo heterozygous sequence variants in the KAT6B gene. Both phenotypes are characterized by significant global developmental delay/intellectual disability, hypotonia, genital abnormalities, and patellar hypoplasia/agenesis. In addition, congenital heart defects, dental abnormalities, hearing loss, and thyroid anomalies are common to both phenotypes. Read More

    Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome.
    Clin Genet 2017 Aug 30. Epub 2017 Aug 30.
    Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, 00146, Rome, Italy.
    Ellis van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with three affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Read More

    Bone marrow failure syndrome caused by homozygous frameshift mutation in the ERCC6L2 gene.
    Clin Genet 2017 Aug 16. Epub 2017 Aug 16.
    PEDEGO Research Unit, University of Oulu, Oulu, Finland.
    Inherited bone marrow failure syndromes (IBMFS) are group of disorders that lead to inadequate production of blood cells. Mutations in genes involved in telomere maintenance, DNA repair, and the cell cycle cause IBMFS. ERCC6L2 gene mutations have been associated with bone marrow failure that includes developmental delay and microcephaly. Read More

    Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication.
    Clin Genet 2017 Aug 12. Epub 2017 Aug 12.
    Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also CNV analysis for genomic changes. Read More

    Bone health and SATB2-associated syndrome.
    Clin Genet 2017 Aug 8. Epub 2017 Aug 8.
    Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
    SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. Read More

    Homozygous Nonsense Mutation in SCHIP1/IQCJ-SCHIP1 Causes a Neurodevelopmental Brain Malformation Syndrome.
    Clin Genet 2017 Aug 8. Epub 2017 Aug 8.
    Neurogenetics Lab, Weill Cornell Medicine, Doha, Qatar.
    We report a consanguineous Arab family with three affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain Magnetic Resonance Imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. Read More

    Diagnosis of monogenic liver diseases in childhood by Next-Generation Sequencing.
    Clin Genet 2017 Aug 4. Epub 2017 Aug 4.
    Department of Kidney, Liver and Metabolic Disease, Division of Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.
    Next-Generation Sequencing (NGS) has opened up novel diagnostic opportunities for children with unidentified, but suspected inherited diseases. We describe our single-center experience with NGS diagnostics in standard clinical scenarios in pediatric hepatology. We investigated 135 children with suspected inherited hepatopathies, where initially no causative pathogenic variant had been identified, with an amplicon-based NGS panel of 21 genes associated with acute and chronic hepatopathies. Read More

    A case of atypical Kabuki syndrome arising from a novel missense variant in HNRNPK.
    Clin Genet 2017 Aug 3. Epub 2017 Aug 3.
    Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
    A novel causative variant (c. 464T>C, p.Leu155Pro) in the heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene. Read More

    Mechanisms of Mendelian dominance.
    Clin Genet 2017 Jul 28. Epub 2017 Jul 28.
    University of Missouri, Division of Biological Sciences, Columbia, MO, 65211.
    Genetic dominance has long been considered as a qualitative reflection of interallelic interactions. Dominance arises from many multiple sources whose unifying theme is the existence of non-linear relationships between the genotypic and phenotypic values. One of the clearest examples are dominant negative mutations (DNMs) in which a defective subunit poisons a macromolecular complex. Read More

    Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.
    Clin Genet 2017 Jul 25. Epub 2017 Jul 25.
    Inserm-UMRS 954 (Nutrition-Genetics-Environmental Risks) and National reference centre for inherited metabolic diseases, University of Lorraine and University Regional Hospital Center, 54500, Vandoeuvre lès Nancy, France.
    Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the one-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTD). GIF and FUT2 are two genes associated with the uptake and blood level of vitamin B12. Read More

    Unilateral Vestibular Schwannoma and Meningiomas in a Patient with PIK3CA-Related Segmental Overgrowth: Co-occurrence of Mosaicism for Two Rare Disorders.
    Clin Genet 2017 Jul 24. Epub 2017 Jul 24.
    Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
    A 28-year-old female with PIK3CA-related segmental overgrowth presented with headaches. She also had a unilateral vestibular schwannoma (VS), as well as three small (<2 cm) meningiomas, which according to the Manchester consensus diagnostic criteria for neurofibromatosis 2 (NF2) is sufficient for a clinical diagnosis. Analysis of blood revealed a mosaic PIK3CA c. Read More

    Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.
    Clin Genet 2017 Jul 14. Epub 2017 Jul 14.
    AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
    Though whole exome sequencing is the gold standard for the diagnosis of neurodevelopmental disorders, it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" constitute an alternative strategy to whole exome sequencing, but its efficiency is poorly known. In this study, we report the experience of two clinical genetic centers using medical exome for diagnosis of neurodevelopmental disorders. Read More

    Whole-exome sequencing is a valuable diagnostic tool for inherited peripheral neuropathies: outcomes from a cohort of 50 families.
    Clin Genet 2017 Jul 14. Epub 2017 Jul 14.
    Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
    The inherited peripheral neuropathies (IPNs) are characterized by marked clinical and genetic heterogeneity and include relatively frequent presentations such as Charcot-Marie-Tooth disease and hereditary motor neuropathy, as well as more rare conditions where peripheral neuropathy is associated with additional features. There are over 250 genes known to cause IPN-related disorders but it is estimated that in ~50% of affected individuals a molecular diagnosis is not achieved. In this study, we examine the diagnostic utility of whole-exome sequencing (WES) in a cohort of 50 families with one or more affected individuals with a molecularly undiagnosed IPN with or without additional features. Read More

    Novel non-neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia.
    Clin Genet 2017 Jul 14. Epub 2017 Jul 14.
    PEDEGO Research Unit, University of Oulu, Oulu, Finland.
    Mitochondria produce adenosine triphosphate (ATP) for energy requirements via the mitochondrial oxidative phosphorylation (OXPHOS) system. One of the hallmarks of cancer is the energy shift towards glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Read More

    Clinical Experience with a Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Test for Five Clinically Significant Microdeletions.
    Clin Genet 2017 Jul 11. Epub 2017 Jul 11.
    Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT.
    Single-nucleotide polymorphism (SNP)-based noninvasive prenatal testing (NIPT) can currently predict a subset of submicroscopic abnormalities associated with severe clinical manifestations. We retrospectively analyzed the performance of SNP-based NIPT in 80,449 referrals for 22q11.2 deletion syndrome and 42,326 referrals for 1p36, cri-du-chat, Prader-Willi, and Angelman microdeletion syndromes over a one-year period, and compared the original screening protocol with a revision that reflexively sequenced high-risk calls at a higher depth of read. Read More

    The impact of epigenomic next-generation sequencing approaches on our understanding of neuropsychiatric disorders.
    Clin Genet 2017 Jul 11. Epub 2017 Jul 11.
    CNRS, UMR7216 Épigénétique et Destin Cellulaire, F-75205 Paris Cedex 13, France.
    Patients suffering from psychiatric disorders have a life span burden, which represents an enormous human, family, social, and economical cost. Several concepts have revolutionized our way of appraising neuropsychiatric disorders (NPDs). They result from a combination of genetic factors and environmental insults, and their etiology finds roots in the neurodevelopmental period. Read More

    Genotype-phenotype study in patients with VCP valosin-containing protein mutations associated with multisystem proteinopathy.
    Clin Genet 2017 Jul 10. Epub 2017 Jul 10.
    Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA.
    Mutations in valosin-containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males, 113 females) from 36 families carrying 15 different VCP mutations. Read More

    Phenotypic spectrum associated with de novo mutations in QRICH1 gene.
    Clin Genet 2017 Jul 10. Epub 2017 Jul 10.
    North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Harrow, UK.
    Rare de novo mutations represent a significant cause of idiopathic developmental delay. The use of NGS has boosted the identification of de novo mutations in an increasing number of novel genes. Here we present three unrelated children with de novo LoF mutations in QRICH1, diagnosed through trio exome sequencing. Read More

    Mining for mitochondrial mechanisms: linking known syndromes to mitochondrial function.
    Clin Genet 2017 Jul 7. Epub 2017 Jul 7.
    Radboud Center for Mitochondrial Disorders, Department of Pediatrics, RadboudUMC, Nijmegen, The Netherlands.
    Mitochondrial disorders (MDs) are caused by defects in one or multiple complexes of the oxidative phosphorylation (OXPHOS) machinery. MDs are associated with a broad range of clinical signs and symptoms, and have considerable clinical overlap with other neuromuscular syndromes. This overlap might be due to involvement of mitochondrial pathways in some of these non-mitochondrial syndromes. Read More

    Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and three novel SLC37A4 variants.
    Clin Genet 2017 Jul 7. Epub 2017 Jul 7.
    Institute of Molecular Genetics and Genetic Engineering, University of Belgrade.
    Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and five Ia patients. Read More

    Integrated Analysis of SNP, CNV and Gene Expression Data in Genetic Association Studies.
    Clin Genet 2017 Jul 7. Epub 2017 Jul 7.
    Computer and Systems Engineering Department, Alexandria University, Alexandria, Egypt.
    Integrative approaches that combine multiple forms of data can more accurately capture CGEway associations and so provide a comprehensive understanding of the molecular mechanisms that cause complex diseases. Association analyses based on SNP genotypes, CNV genotypes, and gene expression profiles are the three most common paradigms used for gene set/ CGEway enrichment analyses. Many work has been done to leverage information from two types of data from these three paradigms. Read More

    Homozygosity for a missense variant in COMP gene associated with severe pseudoachondroplasia.
    Clin Genet 2017 Jul 7. Epub 2017 Jul 7.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP) range from a mild form of multiple epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the phenotypic effect from biallelic COMP variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH in two individuals. Read More

    Phenotypic spectrum of mutations in IBA57, a candidate gene for cavitating leukoencephalopathy.
    Clin Genet 2017 Jul 3. Epub 2017 Jul 3.
    Department of paediatrics, Peking University First Hospital, China.
    IBA57 is involved in the biogenesis of mitochondrial [4Fe-4S] proteins. Eighteen cases with IBA57 mutations have been reported to date. We described a novel phenotype in 11 children with cavitating leukoencephalopathy and summarized the phenotypic spectrum of IBA57 mutations. Read More

    Protein misfolding diseases: prospects of pharmacological treatment.
    Clin Genet 2017 Jul 3. Epub 2017 Jul 3.
    Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, 28049 Madrid/Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Investigación Sanitaria IdiPAZ, Madrid, Spain.
    Protein misfolding has been linked to numerous inherited diseases. Loss- and gain-of-function mutations (common features of genetic diseases) may cause the destabilization of proteins, leading to alterations in their properties and/or cellular location, resulting in their incorrect functioning. Misfolded proteins can, however, be rescued via the use of proteostasis regulators and/or pharmacological chaperones, suggesting that treatments with small molecules might be developed for a range of genetic diseases. Read More

    NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect.
    Clin Genet 2017 Jul 3. Epub 2017 Jul 3.
    Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
    Mitochondrial respiratory chain complex I consists of 44 different subunits and contains three functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. Read More

    Next generation phenotyping in Emanuel and Pallister Killian Syndrome using computer-aided facial dysmorphology analysis of 2D photos.
    Clin Genet 2017 Jun 29. Epub 2017 Jun 29.
    Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany.
    High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of Next Generation Phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely considering of (molecular) cytogenetics during the diagnostic quest. Read More

    A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency.
    Clin Genet 2017 Jun 28. Epub 2017 Jun 28.
    Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Medical Genetics Unit, University of Florence, Florence, Italy.
    Otofaciocervical syndrome is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of otofaciocervical syndrome and a homozygous missense mutation in PAX1 gene has been described. Read More

    A 37-years-old Menkes disease patient - Residual ATP7A activity and early copper administration as key factors in beneficial treatment.
    Clin Genet 2017 Jun 28. Epub 2017 Jun 28.
    Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
    Menkes disease is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving Menkes disease patient (37 years) receiving early-onset and long-term copper treatment. Read More

    A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss.
    Clin Genet 2017 Jun 28. Epub 2017 Jun 28.
    PEDEGO Research Unit, University of Oulu, Oulu, Finland.
    Mutations in GLE1, RNA export mediator (GLE1) gene have previously been shown to cause motor neuron diseases such as Lethal congenital contracture syndrome 1 (LCCS1) and Lethal arthrogryposis with anterior horn cell disease (LAAHD), including arthrogryposis, fetal akinesis and motor neuron loss as common clinical features. The homozygous FinMajor mutation p.T144_E145insPFQ has been described as one of the causes for LCCS1 whereas LAAHD is caused by a heterocompound FinMajor mutation together with p. Read More

    Extension of the phenotype of biallelic loss-of-function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I.
    Clin Genet 2017 Jun 27. Epub 2017 Jun 27.
    Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
    Biallelic mutations in SLC25A46, encoding a modified solute transporter involved in mitochondrial dynamics, have been identified in a wide range of conditions such as hereditary motor and sensory neuropathy with optic atrophy type VIB (OMIM: *610826) and congenital lethal pontocerebellar hypoplasia (PCH). To date, 18 patients from 13 families have been reported, presenting with the key clinical features of optic atrophy, peripheral neuropathy, and cerebellar atrophy. The course of the disease was highly variable ranging from severe muscular hypotonia at birth and early death to first manifestations in late childhood and survival into the fifties. Read More

    Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon.
    Clin Genet 2017 Jun 24. Epub 2017 Jun 24.
    Service de Biochimie Hormonologie, APHP, Paris, France.
    Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in two genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a hyperechoic colon (HEC group) and 39 with a classical postnatal form (CC group). Read More

    Functional Analysis of p.Ala253_Leu254insAsn Mutation in PLS3 Responsible for X-linked Osteoporosis.
    Clin Genet 2017 Jun 24. Epub 2017 Jun 24.
    Center of Translational Medicine, Central Hospital of Zibo, Shandong University, Zibo, China.
    Mutations in Plastin-3 (PLS3) have been identified as a cause of X-linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. Read More

    A genetic epidemiology study of Congenital Adrenal Hyperplasia in Italy.
    Clin Genet 2017 Jun 23. Epub 2017 Jun 23.
    Medical Genetics Unit, Department of Medical and Surgical Sciences, "S.Orsola-Malpighi" University-Hospital, Bologna, Italy.
    Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD-CAH) is an autosomal recessive disorder affecting steroidogenesis, due to mutations in CYP21A2 (6p21.3). 21OHD-CAH neonatal screening is based on 17-hydroxyprogesterone (17OHP) serum levels, showing high type I error rate and low sensitivity to mild CAH forms. Read More

    Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis.
    Clin Genet 2017 Jun 20. Epub 2017 Jun 20.
    Molecular Medicine Research Center & Laboratory of Molecular and Medical Genetics, Dept of Biological Sciences, University of Cyprus, Nicosia-Cuprus.
    Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. Read More

    Increasing awareness and knowledge of lifestyle recommendations for cancer prevention in Lynch Syndrome carriers: randomized controlled trial.
    Clin Genet 2017 Jun 20. Epub 2017 Jun 20.
    Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
    Lynch Syndrome (LS) mutation carriers may reduce their cancer risk by adhering to lifestyle recommendations for cancer prevention. This study tested the effect of providing LS mutation carriers with World Cancer Research Fund (WCRF)-NL health promotion materials on awareness and knowledge of and adherence to these recommendations. In this randomized controlled trial (n = 226), the intervention group (n = 114) received WCRF-NL health promotion materials. Read More

    Further delineation of the phenotype caused by biallelic variants in the WDR4 gene.
    Clin Genet 2017 Jun 15. Epub 2017 Jun 15.
    CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France.
    Microcephalic primordial dwarfisms are a group of rare Mendelian disorders characterized by severe growth retardation and microcephaly. The molecular basis is heterogeneous, with disease-causing genes implicated in different cellular functions. Recently, 2 patients were reported with the same homozygous variant in the WDR4 gene, coding for an enzyme responsible for the m(7) G46 post transcriptional modification of tRNA. Read More

    Fragile X syndrome: an overview and update of the FMR1 gene.
    Clin Genet 2017 Jun 15. Epub 2017 Jun 15.
    Biochemistry and Molecular Genetics Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and the leading form of the monogenic cause of autism. FMR1 premutation is the first single-gene cause of primary ovarian failure (FXPOI) and one of the most common causes of ataxia (FXTAS), multiple additional phenotypes such as fibromyalgia, hypothyroidism, migraine headaches, sleep disturbances, sleep apnea, restless legs syndrome, central pain syndrome, neuropathy and neuropsychiatric alterations has been described. Clinical involvement in men and women carrying the FMR1 premutation currently constitutes a real health problem in the society that should be taken into account. Read More

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