Search Our Scientific Publications & Authors

Ann Hum Genet 2020 May 21. Epub 2020 May 21.

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York.

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services-two single nucleotide polymorphism (SNP)-array based and one sequencing based. Read More

Ann Hum Genet 2020 May 19. Epub 2020 May 19.

Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Read More

Ann Hum Genet 2020 May 13. Epub 2020 May 13.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background: Familial Mediterranean fever is a hereditary inflammatory disorder caused by variants in MEFV. c.2230G>T p. Read More

Ann Hum Genet 2020 May 12. Epub 2020 May 12.

Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, South Korea.

The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K, and H331P). Read More

Ann Hum Genet 2020 May 11. Epub 2020 May 11.

Department of Health Sciences and Sport Medicine, University of Physical Education, Budapest, Hungary.

The aim was to examine the association between the hypoxia-inducible factor-1α (HIF1A) gene and the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene polymorphisms and the endurance/power athlete status and relative aerobic capacity. Another goal of this study was to reveal the connection between GNB3, blood pressure (BP), body composition and body mass index (BMI). Two hundred thirty-eight people participated in this study: 148 elite athletes (men = 107, women = 41) and 90 controls (men = 51, women = 39). Read More

Ann Hum Genet 2020 Apr 12. Epub 2020 Apr 12.

Clinical Genetics Unit, Ospedale Policlinico IRCCS San Martino, Genoa, Italy.

Perrault syndrome is a rare disorder characterized by ovarian dysgenesis, bilateral sensorineural hearing loss and associated with mutations in six mitochondrial proteins. Additional neurological features were also described. Herein, we report on a 27-year-old woman with Perrault syndrome (PS), moderate ataxia and axonal sensory-motor peripheral neuropathy in whom we identified compound heterozygous mutations in the TWNK gene (p. Read More

Ann Hum Genet 2020 May 31;84(3):214-220. Epub 2020 Mar 31.

Department of Medicine, University of California San Diego, La Jolla, California.

The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from this dataset, with 641 genes showing zero variation. Read More

Ann Hum Genet 2020 Mar 12. Epub 2020 Mar 12.

Subdivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.

Introduction: PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype-phenotype correlation and define the most common findings of the syndrome in pediatric patients. Read More

Ann Hum Genet 2020 Mar 12. Epub 2020 Mar 12.

Internal Medicine, Haikou Branch of Yue Yang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (Haikou Hospital of Traditional Chinese Medicine), Hainan, Haikou, China.

The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization-embryo transfer (IVF-ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to amniotic cell culture and chromosome karyotyping and those with abnormal chromosome karyotype were further subjected to C-banding and whole-genome sequencing. Read More

Ann Hum Genet 2020 Mar 2. Epub 2020 Mar 2.

Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

Leigh syndrome is a clinically and radiologically heterogeneous condition with approximately 75 genes, nuclear and mitochondrial, known to be implicated in its pathogenesis. Leigh syndrome due to complex II deficiency constitutes 2% to 7% of these cases. Previously, nine individuals with Leigh syndrome have been reported with pathogenic variants in SDHB, which encodes for the iron-sulfur cluster subunit of mitochondrial respiratory chain complex II. Read More

Ann Hum Genet 2020 May 2;84(3):303-312. Epub 2020 Mar 2.

Department of Genetics, University of Calcutta, Kolkata, India.

Oculocutaneous albinism (OCA) is a group of congenital autosomal recessive disorders with seven known subtypes (OCA1-OCA7) characterized by loss or absence of pigmentation in the skin, hair, and eyes. OCA1, caused by pathogenic variations in the tyrosinase (TYR) gene, has been documented to be the most prevalent subtype across the world including India. In the present study, we recruited 53 OCA-affected individuals from 45 unrelated families belonging to 20 different marriage groups/ethnicities of 15 different districts of West Bengal. Read More

Ann Hum Genet 2020 Mar 2. Epub 2020 Mar 2.

Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.

Purpose: Laotians and Lao Isan are widely spread Lao groups who live in Laos and northeastern Thailand, respectively. We explored the genetic structure between them and other ethnic groups from Thailand to clarify historical patterns of admixture between Tai-Kadai and Austroasiatic speakers, and to expand the forensic reference database for the region.

Subjects And Methods: We combined new genetic data for 554 individuals from 12 populations, typed for 15 autosomal short tandem repeats, with available data from 14 populations from Thailand, for a total of 1,153 raw genotypes belonging to 26 populations. Read More

Ann Hum Genet 2020 Feb 24. Epub 2020 Feb 24.

UCL Genetics Institute, UCL, London, United Kingdom.

Ann Hum Genet 2020 Feb 20. Epub 2020 Feb 20.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

The human dopamine transporter (hDAT) participates in dopamine homeostasis by clearing dopamine from the extracellular space using secondary active transport. Dysregulation of hDAT has been reported to be associated with different neuropsychiatric disorders. Dopamine transporter deficiency syndrome (DTDS) is a complex disease caused by defects in dopamine uptake within the synaptic cleft and patients manifest parkinsonian features. Read More

Ann Hum Genet 2020 May 5;84(3):291-302. Epub 2020 Feb 5.

UCL Genetics Institute, UCL, London, WC1E 6BT, United Kingdom.

Previous studies have implicated common and rare genetic variants as risk factors for late-onset Alzheimer's disease (LOAD). Here, weighted burden analysis was applied to over 10,000 exome-sequenced subjects from the Alzheimer's Disease Sequencing Project. Analyses were carried out to investigate whether rare variants predicted to have a functional effect within a gene were more commonly seen in cases or in controls. Read More

Ann Hum Genet 2020 Jan 20. Epub 2020 Jan 20.

Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China.

Objective: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Read More

Ann Hum Genet 2020 Jan 11. Epub 2020 Jan 11.

UCL Genetics Institute, UCL, London, United Kingdom.

The linkage disequilibrium (LD) score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences among populations and hence that any observed association is the result of a polygenic effect rather than population stratification. This assumption was previously tested only using European cohorts. Read More

Ann Hum Genet 2020 May 19;84(3):205-213. Epub 2019 Dec 19.

MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, Wales.

Preterm birth is associated with short- and long-term impairments affecting physical, cognitive, and neuropsychiatric health. These sequelae, together with a rising preterm birth rate and increased survival, make prematurity a growing public health issue because of the increased number of individuals with impaired health throughout the life span. Although a major contribution to preterm birth comes from environmental factors, it is also modestly heritable. Read More

Ann Hum Genet 2019 Dec 18. Epub 2019 Dec 18.

Yunnan Key laboratory for Basic Research on Bone and Joint Diseases &Yunnan Stem Cell Translational Research Center, Kunming University, Kunming, Yunnan, China.

Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for ∼70% of the OI cases. Read More

Ann Hum Genet 2020 May 16;84(3):271-279. Epub 2019 Dec 16.

Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, Fujian, China.

Background: Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF.

Methods And Materials: The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Read More

Ann Hum Genet 2020 May 13;84(3):280-290. Epub 2019 Dec 13.

Mission Associations Recherche & Société - Inserm Siège, DISC, Paris, France.

Most genome-wide association studies used genetic-model-based tests assuming an additive mode of inheritance, leading to underpowered association tests in case of departure from additivity. The general regression model (GRM) association test proposed by Fisher and Wilson in 1980 makes no assumption on the genetic model. Interestingly, it also allows formal testing of the underlying genetic model. Read More

Ann Hum Genet 2020 May 4;84(3):229-234. Epub 2019 Dec 4.

Department of Histology and Embryology, TOBB University, Ankara, Turkey.

Aim: To share the chorionic villus sampling (CVS) experience of a single surgeon in our institution.

Methods: This retrospective study consists of CVS cases performed between 2000 and 2018. A total of 66 types of indications were classified under two main categories, the screening group (SG) and the inherited disease group (IDG). Read More

Ann Hum Genet 2020 03 4;84(2):185-194. Epub 2019 Dec 4.

Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Ciudad de México, México.

The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-β1 have been associated with type 2 diabetes in different populations but its functional effect is not clear. In this study, we evaluated their effect on the expression of SIRT1 and TGF-β1 in peripheral blood as well as their participation in the formation of DNA-protein complexes in a pancreas-derived cell line. It has been described that SIRT1 and TGF-β1 participate in cell growth and regulation of production and secretion of insulin in the pancreas. Read More

Ann Hum Genet 2020 May 2;84(3):259-270. Epub 2019 Dec 2.

Department of Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0. Read More

Ann Hum Genet 2020 May 21;84(3):235-248. Epub 2019 Nov 21.

Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.

Objective: To investigate the role of ADIPOQ gene variants (-3971G/A rs822396 and +276G/T rs1501299) with type 2 diabetes risk in a North Indian Punjabi population.

Methods: Adiponectin is one of the most abundant circulating adipocytokines in the human body that plays an important role in the metabolic processes and positively regulates energy homeostasis and insulin secretion. Several studies have provided the evidence of adiponectin gene polymorphisms association with type 2 diabetes mellitus (T2DM) in different ethnic populations. Read More

Ann Hum Genet 2020 May 21;84(3):249-258. Epub 2019 Nov 21.

Institute of Hematology and Blood Transfusion, Baku, Azerbaijan.

With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Read More

Ann Hum Genet 2020 03 11;84(2):169-176. Epub 2019 Nov 11.

Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Williams-Beuren syndrome (WBS) is a well-defined multisystem chromosomal disorder that is caused by a chromosome 7q11.23 region heterozygous deletion. We explored prenatal diagnosis of WBS by ultrasound as well as multiple genetic methods to characterize the structural variants of WBS prenatally. Read More

Ann Hum Genet 2020 03 11;84(2):125-140. Epub 2019 Nov 11.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington.

The sequence and assembly of human genomes using long-read sequencing technologies has revolutionized our understanding of structural variation and genome organization. We compared the accuracy, continuity, and gene annotation of genome assemblies generated from either high-fidelity (HiFi) or continuous long-read (CLR) datasets from the same complete hydatidiform mole human genome. We find that the HiFi sequence data assemble an additional 10% of duplicated regions and more accurately represent the structure of tandem repeats, as validated with orthogonal analyses. Read More

Ann Hum Genet 2020 03 7;84(2):161-168. Epub 2019 Nov 7.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Chaoyang, Beijing, China.

KCNQ1, KCNH2, and SCN5A are the most common genes responsible for long QT syndrome and Brugada syndrome. However, the genetic variant frequencies of the three genes in different Chinese disease cohorts are largely unknown. In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing. Read More

Ann Hum Genet 2020 May 5;84(3):221-228. Epub 2019 Nov 5.

Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.

Single-nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome-wide association study (GWAS) data of SLE (1,047 cases and 1,205 controls from a mainland Han Chinese population) to explore the association between the UHRF1BP1 gene and SLE. We conducted a large-scale replication study in an additional independent sample of 3,509 cases and 8,246 controls from a mainland Han Chinese population. Read More

Ann Hum Genet 2020 03 1;84(2):177-184. Epub 2019 Nov 1.

Eye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Objective: The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families.

Materials And Methods: A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis of available family members were used to validate sequencing data and confirm the presence of disease-causing genes. Read More

Ann Hum Genet 2020 03 15;84(2):151-160. Epub 2019 Oct 15.

Andrology Laboratory, Los Andes University, Electronic Microscopic Center, Mérida, Venezuela.

5α-Reductase type 2 deficiency causes a 46,XY disorder of sex development (DSD) characterized by ambiguous external genitalia, rudimentary prostate, and normal internal genitalia. The disease prevalence worldwide is low, but in a small and isolated village of the Venezuelan Andes, a higher incidence has been found. DNA analysis of the SRD5A2 gene was performed in three inbred affected individuals clinically diagnosed with DSD. Read More

Ann Hum Genet 2020 03 9;84(2):195-200. Epub 2019 Oct 9.

Department of Human Genetics, Hannover Medical School, Hannover, Germany.

Wilson's disease is an autosomal recessive disorder resulting from copper excess. Some patients with clinical Wilson's disease symptoms exhibit no or only heterozygous pathogenic variants in the coding region of the disease-causing ATP7B gene. Therefore, the ATP7B promoter region is of special interest. Read More

Ann Hum Genet 2020 01 3;84(1):54-71. Epub 2019 Oct 3.

Department of Anatomy, Dongguk University Graduate School of Medicine, Gyeongju, Republic of Korea.

Mutations in the SMPX gene can disrupt the regular activity of the SMPX protein, which is involved in the hearing process. Recent reports showing a link between nonsynonymous single-nucleotide polymorphisms (nsSNPs) in SMPX and hearing loss, thus classifying deleterious SNPs in SMPX will be an uphill task before designing a more extensive population study. In this study, damaging nsSNPs of SMPX from the dbSNP database were identified by using 13 bioinformatics tools. Read More

Ann Hum Genet 2020 03 3;84(2):201-204. Epub 2019 Oct 3.

Department of Pediatrics, Division of Child Neurology, Montreal Children's Hospital, McGill University Health Centre, Montreal, PQ, Canada.

The Xq26 locus has importance in human growth with multiple genes and regions playing important roles, which potentially leads to macrosomia or microsomia if disrupted. One region of Xq26.2 comprises the genes GPC3 and GPC4; deletion or duplication of this region has been recently been shown to result in overgrowth, specifically Simpson-Golabi-Behmel syndrome. Read More

Ann Hum Genet 2020 01 30;84(1):102-106. Epub 2019 Sep 30.

Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran.

Osteosclerotic metaphyseal dysplasia (OSMD) is a very rare autosomal-recessive disorder and a distinctive type of osteopetrosis, characterized mainly by skeletal fractures and deformity, osteosclerosis, and sometimes hypotonia, developmental delay, and seizures. Sequence variants in the leucine-rich repeat kinase 1 (LRRK1) gene underlying OSMD have been reported previously. In the present study, we investigated a 14-year-old girl suspected with OSMD in a consanguineous family of Iranian origin segregating the disease in an autosomal-recessive manner. Read More

Ann Hum Genet 2020 03 1;84(2):114-124. Epub 2019 Oct 1.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland.

Diabetes mellitus (DM) is a heterogeneous group of disorders whose common trait is chronic hyperglycemia. Gestational diabetes mellitus (GDM) is one of the subtypes of DM that manifests during pregnancy. It is believed that 2%-5% of pregnancies worldwide are complicated with GDM, with the prevalence having significantly increased over the last decade. Read More

Ann Hum Genet 2020 03 1;84(2):141-150. Epub 2019 Oct 1.

Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil.

The purpose of the present study was to explore the ability of the total genotype score (TGS) for evaluation of the polygenic profile of elite athletes. Data from a Brazilian athlete cohort were used in this study, which included 368 athletes and 818 nonathletes. The TGS targeted to power athletes was computed using from two to 10 associated polymorphisms. Read More

Ann Hum Genet 2020 01 11;84(1):37-45. Epub 2019 Sep 11.

Department of Genetics, Faculty of Medical Sciences , Tabriz University of Medical Sciences, Tabriz, Iran.

Background: Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations.

Methods And Materials: 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Read More

Ann Hum Genet 2020 03 11;84(2):107-113. Epub 2019 Sep 11.

Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Mutations in the GJB2 gene are a main cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be ∼16% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our two previous publications and data from searching other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in central Iran. Read More

Ann Hum Genet 2020 01 8;84(1):46-53. Epub 2019 Sep 8.

State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200438, China.

Intellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease-causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including embryo formation, nerve cell growth, and cancer cell metastasis, and very recently it has been suggested that N-acetylneuraminic acid synthase-mediated synthesis of sialic acid is required for brain and skeletal development. Read More

Ann Hum Genet 2020 01 4;84(1):72-79. Epub 2019 Sep 4.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, P. R. China.

Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel insights into the etiology of complex human disease. Read More

Ann Hum Genet 2020 01 30;84(1):97-101. Epub 2019 Aug 30.

Department of Pediatric Dentistry, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, People's Republic of China.

Mutations of MSX1 have been associated with nonsyndromic hypodontia. To seek the causal gene mutation sites in a family with nonsyndromic oligodontia, whole-exome sequencing (WES) was performed to seek the causative locus of the family. The candidate mutation was further identified by Sanger sequencing afterward. Read More

Ann Hum Genet 2020 01 16;84(1):11-28. Epub 2019 Aug 16.

Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Introduction And Objectives: Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical-radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still less than 50%. Read More

Ann Hum Genet 2020 01 8;84(1):1-10. Epub 2019 Aug 8.

Neuroimmunological Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

No genetic modifiers of multiple sclerosis (MS) severity have been independently validated, leading to a lack of insight into genetic determinants of the rate of disability progression. We investigated genetic modifiers of MS severity in prospectively acquired training (N = 205) and validation (N = 94) cohorts, using the following advances: (1) We focused on 113 genetic variants previously identified as related to MS severity; (2) We used a novel, sensitive outcome: MS Disease Severity Scale (MS-DSS); (3) Instead of validating individual alleles, we used a machine learning technique (random forest) that captures linear and complex nonlinear effects between alleles to derive a single Genetic Model of MS Severity (GeM-MSS). The GeM-MSS consists of 19 variants located in vicinity of 12 genes implicated in regulating cytotoxicity of immune cells, complement activation, neuronal functions, and fibrosis. Read More

Ann Hum Genet 2020 01 8;84(1):29-36. Epub 2019 Aug 8.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Thalassemia Research, Nanning, Guangxi Province, China.

Increased levels of fetal hemoglobin (HbF: α2γ2) can ameliorate the clinical severity of the β-hemoglobinopathies. Microarray analysis represents a powerful approach to identify novel genetic factors regulating the γ-globin gene. Gene expression profiling was previously performed on 14 individuals with high or normal HbF levels to identify the genetic factors that control γ-globin gene expression. Read More

Ann Hum Genet 2019 11 2;83(6):397-404. Epub 2019 Aug 2.

Department of Ophthalmology and Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College of Fudan University; NHC Key Laboratory of Myopia (Fudan University), Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.

Background: Pterygium and meibomian gland dysfunction (MGD) are two clinically correlated ocular diseases. We propose to investigate the shared gene signature between pterygium and MGD.

Methods: Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database. Read More

Ann Hum Genet 2019 11 29;83(6):445-453. Epub 2019 Jul 29.

Department of Nephrology, Shanghai Changhai Hospital, Shanghai, China.

Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Read More

Ann Hum Genet 2020 01 29;84(1):87-91. Epub 2019 Jul 29.

Institute of Cell and Neurobiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Biallelic mutations in the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2 cause autosomal recessive primary microcephaly type 3 (MCPH3). MCPH is characterized by intellectual disability and microcephaly at birth, classically without further organ involvement. Only recently, congenital cataracts were reported in four patients of one pedigree with MCPH3. Read More

Ann Hum Genet 2020 01 26;84(1):92-96. Epub 2019 Jul 26.

Center of Translational Medicine, Central Hospital of Zibo, Shandong University, Zibo, China.

Osteoporosis is a complex bone metabolic disorder. Genetic factors play an important role in the development of osteoporosis. Mutations in more than 15 genes have been identified to be responsible for osteoporosis to date. Read More