自引率: 3.5%
被引量: 4253
通过率: 暂无数据
审稿周期: 2.5
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国人发稿量: 21
投稿须知/期刊简介:
The Journal of Human Genetics is a leading international journal publishing articles on human genetics including medical genetics and human genome analysis. We welcome papers on any aspects of human genetics including gene cloning and mapping linkage analysis mutational analysis evolution cancer genetics and gene therapy as well as genetic and functional analysis of animal models of disease or behavior. The journal also welcomes clinical or cytogenetic case reports as well as reports of genetic polymorphism of biologically important genes novel mutations found in patients with hereditary diseases or in cancer cells and population genetics. Papers will be considered for publication in the following categories: 1. Minireviews 2. Original articles 3. Short communications (including case reports and polymorphism reports) 4. Announcement The editors reserve the right to decide in which section an article will appear.
期刊描述简介:
The Journal of Human Genetics is a leading international journal, publishing articles on human genetics, including medical genetics and human genome analysis. Coverage includes all aspects of human genetics, including gene cloning and mapping, linkage analysis, mutational analysis, evolution, cancer genetics, and gene therapy, as well as genetic and functional analysis of animal models of disease or behavior. The journal also presents clinical or cytogenetic case reports, as well as reports of genetic polymorphism of biologically important genes, novel mutations found in patients with hereditary diseases or in cancer cells, and population genetics. Articles are presented in the form of Articles, Brief Communications, Review Articles, Correspondences, Editorials, and Comments. The journal is associated with the Japan Society of Human Genetics.
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Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history.
Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.
被引量：- 发表：1970
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Investigating common mutations in ATP7B gene and the prevalence of Wilson's disease in the Thai population using population-based genome-wide datasets.
Wilson's disease (WD) is a rare metabolic disorder caused by variations in the ATP7B gene. It usually manifests hepatic, neurologic, and psychiatric symptoms due to excessive copper accumulation. The prevalence of WD and its common variants differ across populations. This study aimed to examine these aspects of WD within the Thai population, where information has been limited. We reviewed ClinVar and the Wilson Disease Mutation Database, organizing variants classified as pathogenic or likely pathogenic in one or both databases as "relaxed" and "strict" lists. Allele frequencies were estimated from genotyping array data (Asian Screening Array: ASA; Illumina Corp, CA) of 6291 Thai subjects, which also underwent genotype imputation. The prevalence of WD in the Thai population was estimated assuming Hardy-Weinberg Equilibrium. The strict list yielded a prevalence of 1/24,128 (carrier frequency=1/78), while the relaxed list yielded a prevalence of 1/9971 (carrier frequency=1/50). The most common WD variants in Thai subjects were c.2333 G > T, c.3443 T > C, and c.813 C > A from the strict list, and c.3316 G > A and c.2605 G > A from the relaxed list. The ASA chip covered approximately 59 and 24% of WD variants from the strict and relaxed lists, respectively. Based on the estimated prevalence, a carrier screening program for WD is not currently required in Thailand. However, as genotyping services become more affordable and accessible, such a program would facilitate early identification, treatment, and prevention of WD.
被引量：- 发表：1970
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Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants.
Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis. Using whole-exome sequencing (WES), we identified compound heterozygous variants of the SCN4A gene encoding the voltage-gated sodium channel of the skeletal muscle (hNav1.4), c.2429T>A p.L810Q and c.4556T>C p.F1519S, in all three deceased infants. A functional analysis conducted using the whole-cell patch-clamp technique revealed loss-of-function defects in both variant channels, with F1519S exhibiting a complete loss of ionic current and L810Q showing a reduced channel opening. These findings support the pathogenicity of SCN4A variants in NIHF and underscore the significance of functional studies in elucidating genotype-phenotype correlations. Furthermore, our study emphasizes the diagnostic value of WES in cases of NIHF in where standard genetic testing fails to identify causative variants.
被引量：- 发表：1970
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Contribution of rare variants to heritability of a disease is much greater than conventionally estimated: modification of allele distribution model.
"Missing heritability" is a current problem in human genetics. I previously reported a method to estimate heritability of a polymorphism (hp2) for a common disease without calculating the genetic variance under dominant and the recessive models. Here, I extend the method to the co-dominant model and carry out trial calculations of hp2. I also calculate hp2 applying the allele distribution model originally reported by Pawitan et al. for comparison as a conventional method. But unexpectedly, hp2 calculated for rare variants with high odds ratios was much higher than the calculated values with the allele distribution model. Also, while examining the basis for the difference in calculated hp2, I noticed that conventional methods use the allele frequency (AF) of a variant in the general population to calculate the genetic variance of that variant. However, this implicitly assumes that the unaffected are included among the phenotypes of the disease - an assumption that is inconsistent with case-control studies in which unaffected individuals belong to the control (unaffected) group. Therefore, I modified the allele distribution model by using the AF in the patient population. Consequently, the hp2 of rare variants calculated with the modified allele distribution model was quite high. Recalculating hp2 of several rare variants reported in the literature with the modified allele distribution model yielded results were 3.2 - 53.7 times higher than the hp2 calculated with the original allele distribution model. These results suggest that the contribution of rare variants to heritability of a disease has been considerably underestimated.
被引量：- 发表：1970
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A novel homozygous nonsense variant of STX2 underlies non-obstructive azoospermia in a consanguineous Chinese family.
Male infertility is a widespread population health concern, causing various degrees of adverse fertility outcomes. We determined the genetic cause of an infertile male from a consanguineous family, expanding the mutant spectrum of male infertility. A non-obstructive azoospermia (NOA) patient was recruited, and histological type of human testicular tissue of the patient categorized as maturation arrest. We identified a novel loss-of-function variant of syntaxin 2 (STX2) (c.142C>T:p.Gln48*) by performing Whole-exome sequencing (WES) on the NOA patient from a consanguineous Chinese family. Sanger sequencing confirmed the p.Gln48* variant was maternally and paternally inherited. The variant was predicted to be deleterious and resulted in aberrant changes to structure and function of STX2 by In silico analysis. In summary, we reported for the first time that a nonsense variant occurred in the exon region of STX2 in an infertile male presenting with NOA, which was beneficial for diagnosis and therapies of NOA.
被引量：- 发表：1970
