Human Genetics (HUM GENET)

Publisher: Springer Verlag

Journal description

Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal welcomes articles in the areas of Gene structure and organization Gene expression Mutation detection and analysis Linkage analysis and genetic mapping Physical mapping Cytogenetics and Genomic Imaging Genome structure and organisation Disease association studies Molecular diagnostics Genetic epidemiology Evolutionary genetics Developmental genetics Genotype-phenotype relationships Molecular genetics of tumorigenesis Genetics of complex diseases and epistatic interactions and Bioinformatics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless they report entirely novel and unusual aspects of a topic clinical case reports cytogenetic case reports papers on descriptive population genetics articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described will normally not be accepted. The Journal will not normally consider for publication manuscripts that report merely the isolation map position structure and tissue expression profile of a gene of unknown function unless the gene is of unusual interest or is a candidate gene involved in a human trait or disorder. Data on novel pathological mutations may be submitted to Human Genetics Online the electronic mutation data submission system administered by Springer-Verlag (

Current impact factor: 4.82

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 4.824
2013 Impact Factor 4.522
2012 Impact Factor 4.633
2011 Impact Factor 5.069
2010 Impact Factor 5.047
2009 Impact Factor 4.523
2008 Impact Factor 4.042
2007 Impact Factor 3.974
2006 Impact Factor 3.662
2005 Impact Factor 4.331
2004 Impact Factor 4.328
2003 Impact Factor 4.022
2002 Impact Factor 3.429
2001 Impact Factor 3.209
2000 Impact Factor 3.422
1999 Impact Factor 3.145
1998 Impact Factor 2.826
1997 Impact Factor 2.662
1996 Impact Factor 2.455
1995 Impact Factor 2.551
1994 Impact Factor 2.758
1993 Impact Factor 2.666
1992 Impact Factor 2.877

Impact factor over time

Impact factor

Additional details

5-year impact 4.52
Cited half-life 9.20
Immediacy index 1.47
Eigenfactor 0.02
Article influence 1.73
Website Human Genetics website
Other titles Human genetics (Online), Hum genet
ISSN 0340-6717
OCLC 41232248
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification

Publications in this journal

  • Larissa Lazzarini Furlan · Fernando Augusto Lima Marson · José Dirceu Ribeiro · Carmen Sílvia Bertuzzo · João Batista Salomão Junior · Dorotéia Rossi Silva Souza
    [Show abstract] [Hide abstract] ABSTRACT: The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality.
    No preview · Article · May 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: In the last decade, there has been a flood of new technology in the sequencing arena. The onset of next-generation sequencing (NGS) technology has resulted in the vast increase in genetic diagnostic testing available to the ordering physician. Whole exome sequencing (WES) has become available as a diagnostic test performed in certified clinical laboratories. This has led to increased presence in the diagnostic marketplace, increased consumer awareness, and the question has been raised by various stakeholders to whether there is sufficient stringent regulation of WES and other NGS-based tests. We discuss the various WES services currently available in the marketplace, current regulation of WES as a laboratory developed test, the proposed FDA involvement in its oversight as well as the response of various laboratory groups that provide these diagnostic services. Overall, a rigorous process oversight and assessment of inter-lab reproducibility is strongly warranted for WES as it is used as a diagnostic test, but regulation should be mindful of the excessive administrative burden on academic and smaller diagnostic laboratories.
    No preview · Article · May 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Christianson syndrome (OMIM 300243), caused by mutations in the X-linked SLC9A6 gene, is characterized by severe global developmental delay and intellectual disability, developmental regression, epilepsy, microcephaly and impaired ocular movements. It shares many common features with Angelman syndrome. Carrier females have been described as having learning difficulties with mild to moderate intellectual disability, behavioural issues and psychiatric illnesses. There is little literature on the carrier female phenotype of Christianson syndrome. We describe a large extended family with three affected males, four carrier females, one presumed carrier female and one obligate carrier female with a c.190G>T, p.E64X mutation known to cause a premature stop codon in SLC9A6. We characterize and expand the clinical phenotype of female SLC9A6 mutation carriers by comparing our described family with female carriers previously discussed in the literature. In particular, we highlight the neurodevelopmental and psychiatric phenotypes observed in our family and previous reports.
    No preview · Article · May 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Molybdenum cofactor (MoCo) deficiency is a rare, autosomal-recessive disorder, mainly caused by mutations in MOCS1 (MoCo deficiency type A) or MOCS2 (MoCo deficiency type B) genes; the absence of active MoCo results in a deficiency in all MoCo-dependent enzymes. Patients with MoCo deficiency present with neonatal seizures, feeding difficulties, severe developmental delay, brain atrophy and early childhood death. Although substitution therapy with cyclic pyranopterin monophosphate (cPMP) has been successfully used in both Mocs1 knockout mice and in patients with MoCo deficiency type A, there is currently no Mocs2 knockout mouse and no curative therapy for patients with MoCo deficiency type B. Therefore, we generated and characterized a Mocs2-null mouse model of MoCo deficiency type B. Expression analyses of Mocs2 revealed a ubiquitous expression pattern; however, at the cellular level, specific cells show prominent Mocs2 expression, e.g., neuronal cells in cortex, hippocampus and brainstem. Phenotypic analyses demonstrated that Mocs2 knockout mice failed to thrive and died within 11 days after birth. None of the tested MoCo-dependent enzymes were active in Mocs2-deficient mice, leading to elevated concentrations of purines, such as hypoxanthine and xanthine, and non-detectable levels of uric acid in the serum and urine. Moreover, elevated concentrations of S-sulfocysteine were measured in the serum and urine. Increased levels of xanthine resulted in bladder and kidney stone formation, whereas increased concentrations of toxic sulfite triggered neuronal apoptosis. In conclusion, Mocs2-deficient mice recapitulate the severe phenotype observed in humans and can now serve as a model for preclinical therapeutic approaches for MoCo deficiency type B.
    No preview · Article · May 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an important axis of genetic heterogeneity contributing to expression variability among affected individuals has been overlooked. To this end, we develop a new gene expression analysis method-aberrant gene expression analysis, based on the multivariate distance commonly used for outlier detection. Our method detects the discrepancies in gene expression dispersion between groups and identifies genes with significantly different expression variability. Using this new method, we re-visited RNA sequencing data generated from post-mortem brain tissues of 47 ASD and 57 control samples. We identified 54 functional gene sets whose expression dispersion in ASD samples is more pronounced than that in controls, as well as 76 co-expression modules present in controls but absent in ASD samples due to ASD-specific aberrant gene expression. We also exploited aberrantly expressed genes as biomarkers for ASD diagnosis. With a whole blood expression data set, we identified three aberrantly expressed gene sets whose expression levels serve as discriminating variables achieving >70 % classification accuracy. In summary, our method represents a novel discovery and diagnostic strategy for ASD. Our findings may help open an expression variability-centered research avenue for other genetically heterogeneous disorders.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Clinical exome sequencing has clearly improved our ability as clinicians to identify the cause of a wide variety of disorders. Prior to exome sequencing, a majority of patients with apparent syndromes never received a specific molecular genetic diagnosis despite extensive diagnostic odysseys. Even for those receiving an answer to the question of what caused their disorder, the diagnostic odyssey often spanned years to decades. Determining the particular genetic cause in an individual patient can be challenging due to inherent phenotypic and genetic heterogeneity of disease, technical limitations of testing or both. Blended phenotypes, due to multiple monogenic disorders in the same patient, are true dilemmas for traditional genetic evaluations, but are increasingly being diagnosed through clinical exome sequencing. New sequencing technologies have increased the proportion of patients receiving molecular diagnoses, while significantly shortening the time scale, providing multiple benefits for the health-care team, patient and family.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value < 0.05, for genes associated with GP, SUI, abdominal hernia, varicose veins and hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Intratumor heterogeneity within individual cancer tissues underlies the numerous phenotypes of cancer. Tumor subclones ultimately affect therapeutic outcomes due to their distinct molecular features. Drug-resistant subclones are present at a low frequency in tissues at the time of biopsy, but can also arise as a result of acquired somatic mutations. A number of different approaches have been utilized to understand the nature of intratumor heterogeneity. Clonal analysis using whole exome or genome sequencing data can help monitor subclones in the context of tumor progression. Multiregional biopsies permit the molecular characterization of subclones within tumors. Deep sequencing has also provided researchers with the ability to measure the low allele fraction variant within a small number of cells. Ultimately, single-cell sequencing will enable the identification of every minor population within a tumor microenvironment. In the clinical context, the ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Intellectual disability (ID) is one of the most common disabilities and, although many genes have been implicated in its etiology, the genetic heterogeneity of ID continues to expand. The purpose of the study was to describe a novel autosomal recessive non-syndromic ID locus. Autozygome and linkage analysis, and exome sequencing followed by RNA and protein analysis of the candidate disease gene were performed. We describe two multiplex consanguineous families with non-syndromic ID phenotype, which maps to a critical linkage locus on 3q26. Exome sequencing of the index in each family revealed the same homozygous truncating mutation in TNIK that results in complete loss of the protein. TNIK is a kinase with a well-established role in dendrite development and synaptic transmission. The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik −/− phenotype in the murine model. Our data strongly implicate TNIK deficiency in the causation of ID in humans.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Microdeletion syndromes are frequent causes of neuropsychiatric disorders leading to intellectual disability as well as autistic features accompanied by epilepsy and craniofacial anomalies. From comparative deletion mapping of the smallest microdeletion to date at 12q24.31, found in a patient with overlapping clinical features of 12q24.31 microdeletion syndrome, we narrowed the putative critical region to 445 kb containing seven genes, one microRNA, and one non-coding RNA. Zebrafish in situ hybridization and comprehensive transcript analysis of annotated genes in the panels of human organ and brain suggest that these are all candidates for neurological phenotypes excluding the gene HPD. This is also corroborated by synteny analysis revealing the conservation of the order of these six candidate genes between humans and zebrafish. Among them, we propose histone demethylase KDM2B and histone methyltransferase SETD1B as the two most plausible candidate genes involved in intellectual disability, autism, epilepsy, and craniofacial anomalies. These two chromatin modifiers located approximately 224 kb apart were both commonly deleted in six patients, while two additional patients had either KDM2B or SETD1B deleted. The four additional candidate genes (ORAI1, MORN3, TMEM120B, RHOF), a microRNA MIR548AQ, and a non-coding RNA LINC01089 are localized between KDM2B and SETD1B. The 12q24.31 microdeletion syndrome with syndromic intellectual disability extends the growing list of microdeletion syndromes and underscores the causative roles of chromatin modifiers in cognitive and craniofacial development.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Sarcoidosis is a multisystem granulomatous disorder that causes significant morbidity. Genetic factors contribute to sarcoidosis risks. In this study, we investigated whether copy number variations (CNVs) of FCGR3A (coding for FcγRIIIA) and FCGR3B (coding for FcγRIIIB) genes are associated with sarcoidosis susceptibility and whether the expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils are altered in sarcoidosis patients. TaqMan real-time PCR assays were used to analyze the CNV of FCGR3A and FCGR3B genes. FCGR3A and FCGR3B CNV genotypes were compared between 671 biopsy-proven sarcoidosis patients and the same number of healthy controls matched with age, sex, race, and geographic area from the ACCESS (A Case Control Etiologic Study of Sarcoidosis) cohort. Flow cytometry analyses were used to determine expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils in phenotype analyses. We found that FCGR3A CNVs were significantly associated with sarcoidosis in females (CN = 1 vs. CN = 2 logistic regression adjusted for sex and race, OR 4.0156, SE = 2.2784, P = 0.0143; CN = 3 vs. CN = 2 logistic regression adjusted for sex and race, OR 2.8044, SE = 1.1065, P = 0.0090), suggesting that FCGR3A gene abnormality influences sarcoidosis development in a gender-specific manner. Furthermore, FcγRIIIA expressions were significantly decreased on NK cells from sarcoidosis patients compared to those from healthy controls (P = 0.0007). Additionally, low FCGR3B CN was associated with sarcoidosis (CN <2 vs. CN = 2 logistic regression adjusted for sex and race, OR 1.5025, SE = 0.2682, P = 0.0226), indicating that the functions of FCGR3B gene may also contribute to the pathogenesis of sarcoidosis. We conclude that FCGR3A CNVs are a major risk factor for female sarcoidosis and FCGR3B CNVs may also affect the development of sarcoidosis.
    No preview · Article · Apr 2016 · Human Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Intellectual disability is a common and highly heterogeneous disorder etiologically. In a multiplex consanguineous family, we applied autozygosity mapping and exome sequencing and identified a novel homozygous truncating mutation in PUS3 that fully segregates with the intellectual disability phenotype. Consistent with the known role of Pus3 in isomerizing uracil to pseudouridine at positions 38 and 39 in tRNA, we found a significant reduction in this post-transcriptional modification of tRNA in patient cells. Our finding adds to a growing list of intellectual disability disorders that are caused by perturbation of various tRNA modifications, which highlights the sensitivity of the brain to these highly conserved processes.
    No preview · Article · Apr 2016 · Human Genetics