Abstract:
:Heterozygous pathogenic variants in SLC12A2 are reported in patients with nonsyndromic hearing loss. Recently, homozygous loss-of-function variants have been reported in two patients with syndromic intellectual disability, with or without hearing loss. However, the clinical and molecular spectrum of SLC12A2 disease has yet to be characterized and confirmed. Using whole-exome sequencing, we detected a homozygous splicing variant in four patients from two independent families with severe developmental delay, microcephaly, respiratory abnormalities, and subtle dysmorphic features, with or without congenital hearing loss. We also reviewed the reported cases with pathogenic variants associated with autosomal dominant and recessive forms of the SLC12A2 disease. About 50% of the cases have syndromic and nonsyndromic congenital hearing loss. All patients harboring the recessive forms of the disease presented with severe global developmental delay. Interestingly, all reported variants are located in the c-terminal domain, suggesting a critical role of this domain for the proper function of the encoded co-transporter protein. In conclusion, our study provides an additional confirmation of the autosomal recessive SLC12A2 disease.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Bilal Shamsi M,Saleh M,Almuntashri M,Alharby E,Samman M,Peake RWA,Al-Fadhli FM,Alasmari A,Faqeih EA,Almontashiri NAMdoi
10.1038/s10038-021-00904-2subject
Has Abstractpub_date
2021-01-27 00:00:00eissn
1434-5161issn
1435-232Xpii
10.1038/s10038-021-00904-2pub_type
杂志文章abstract::Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished b...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.103
更新日期:2013-12-01 00:00:00
abstract::Several genetic loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, ADAMTS9, VEGFA and HHEX-IDE) were identified to be significantly related to the risk of type 2 diabetes and quantitative metabolic traits in European populations. Here, we aimed to evaluate the impacts of these novel loci on type 2 diabetes risk in a population-...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.117
更新日期:2010-12-01 00:00:00
abstract::A full-length cDNA encoding a novel protein was isolated and sequenced from a human placental cDNA library. This cDNA consists of 1,735 base pairs and has a predicted open reading frame (ORF) encoding 354 amino acids. It possesses a putative signal sequence, a long extracellular domain, a transmembrane region, a short...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070013
更新日期:2000-01-01 00:00:00
abstract::Schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In additio...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.24
更新日期:2010-05-01 00:00:00
abstract::Multiple testing occurs commonly in genome-wide association studies with dense SNPs map. With numerous SNPs, not only the genotyping cost and time increase dramatically, many family wise error rate (FWER) controlling methods may fail for being too conservative and of less power when detecting SNPs associated with dise...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0159-9
更新日期:2007-01-01 00:00:00
abstract::Genetic testing for BRCA1/2 mutations has become the standard clinical practice. Recent findings suggest the clinical significance of multigene panel testing of BRCA1/2 and other cancer-related genes. However, the clinical features of patients with breast cancer with germline mutations identified using multigene panel...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0729-7
更新日期:2020-07-01 00:00:00
abstract::A recent association study suggested that the His113 variant of microsomal epoxide hydrolase (mEPHX) may confer a risk for development of emphysema, presumably by increasing susceptibility to smoking injury. Before considering a possible role of this enzyme in pulmonary disease, we attempted to characterize the geneti...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170116
更新日期:2001-01-01 00:00:00
abstract::DNA-repair pathways are critical for maintaining the integrity of the genetic material by protecting against mutations due to exposure-induced damages or replication errors. Polymorphisms in the corresponding genes may be relevant in genetic epidemiology by modifying individual cancer susceptibility or therapeutic res...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0097-0
更新日期:2003-01-01 00:00:00
abstract::Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene on chromosome 6p12. The longest continuous open reading frame comprises 66 exons encoding a novel 4,074 aa multidomain integral membrane protein (polyductin/fibrocystin) of unknown f...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0022-4
更新日期:2006-01-01 00:00:00
abstract::Our mtDNA and Y chromosome studies lead to the conclusion that the Andamanese "Negrito" mtDNA lineages have survived in the Andaman Islands in complete genetic isolation from other South and Southeast Asian populations since the initial settlement of the region by the out-of-Africa migration. In order to obtain a robu...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0026-0
更新日期:2006-01-01 00:00:00
abstract::The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GD...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2008.13
更新日期:2009-02-01 00:00:00
abstract::Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the s...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2008.16
更新日期:2009-02-01 00:00:00
abstract::The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.15
更新日期:2014-05-01 00:00:00
abstract::Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings ar...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.2
更新日期:2016-06-01 00:00:00
abstract::Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. More than 90% of CAH cases are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200077
更新日期:2002-01-01 00:00:00
abstract::The prefrontal cortex has been implicated in schizophrenia (SZ) and affective disorders by gene expression studies. Owing to reciprocal connectivity, the thalamic nuclei and their cortical fields act as functional units. Altered thalamic gene expression would be expected to occur in association with cortical dysfuncti...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.93
更新日期:2009-11-01 00:00:00
abstract::Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0301-5
更新日期:2005-01-01 00:00:00
abstract::alpha-1-Antichymotrypsin (ACT) is a plasma protease inhibitor belonging to the serpine superfamily; it has many functions. and thus qualitative change in ACT is likely to result in specific diseases. We previously reported a variant AACT (ACT Isehara-1, Met389Val, A1252G) in patients with ischemic cerebrovascular dise...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170125
更新日期:2001-01-01 00:00:00
abstract::In mammals, X-linked gene products can be dosage compensated between males and females by inactivation of one of the two X chromosomes in the developing female embryos. X inactivation choice is usually random in embryo mammals, but several mechanisms can influence the choice determining skewed X inactivation. As a con...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0049-6
更新日期:2006-01-01 00:00:00
abstract::Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding the abnormalities of the HMBS gene, many different mutations have been reported worldwide; however, few families from Japan have been studied. In this work, we ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070038
更新日期:2000-01-01 00:00:00
abstract::We found that a subject with Cockayne syndrome type A was a compound heterozygote for two new mutations in CKN1 (MIM 216400): a missense mutation (A205P) and a nonsense (E13X) mutation. We also identified and characterized a new common single nucleotide polymorphism in CKN1 in five groups. ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0107-2
更新日期:2004-01-01 00:00:00
abstract::Prader-Willi syndrome (PWS) is primarily caused by deletions involving the paternally derived imprinted region at chromosome 15q11.2-q13 and maternal uniparental disomy 15 (upd(15)mat). The underlying mechanisms for upd(15)mat include trisomy rescue (TR), gamete complementation (GC), monosomy rescue and post-fertiliza...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.59
更新日期:2011-08-01 00:00:00
abstract::WNK lysine-deficient protein kinase 1 (WNK1) is a member of the WNK family of serine/threonine kinases with no lysine (K), and these kinases have been implicated as important modulators of salt homeostasis in the kidney. It is well known that high dietary sodium and low dietary potassium have been implicated in the et...
journal_title:Journal of human genetics
pub_type: 杂志文章,随机对照试验
doi:10.1038/jhg.2009.64
更新日期:2009-08-01 00:00:00
abstract::The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian po...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.99
更新日期:2010-11-01 00:00:00
abstract::Mutations in BRCA genes elevate risk for breast and ovarian cancer. These mutations are population specific. As there are no data on BRCA mutation screening on larger number of probands in Serbia to date, aim of this study was to determine types and frequencies of BRCA mutations in individuals from high-risk families ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.30
更新日期:2013-08-01 00:00:00
abstract::We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in environmental endocrine disruptors (EEDs) metabolism might influence the risk of male genital malformations. In this study, we explored for association between 384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1,...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.48
更新日期:2012-07-01 00:00:00
abstract::Recently, haplotype-based association studies have become popular for detecting disease-related or drug-response-associated genes. In these studies, it has been gradually recognized that a haplotype block structure is important. A rational and automatic method for identifying the haplotype block structure from SNP dat...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0176-8
更新日期:2007-01-01 00:00:00
abstract::The mechanism of speciation has remained largely unresolved, and hominoid evolutionary history based on chromosome rearrangements has been continuously challenged. The recent availability of the human-derived chromosome 1-specific midisatellite (D1Z2) and chromosome X-specific macrosatellite (DXZ4) DNA sequence probes...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050108
更新日期:1999-01-01 00:00:00
abstract::Mutations of OCRL cause Lowe syndrome, which is characterised by congenital cataracts, infantile hypotonia with mental retardation, and renal tubular dysfunction and Dent-2 disease, which only affects the kidney. While few patients with an intermediate phenotype between these diseases have been reported, the mechanism...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0773-3
更新日期:2020-10-01 00:00:00
abstract::Two-color fluorescence in situ hybridization (FISH) analysis using human chromosome arm-specific telomeric probes (telomeric probes) was used successfully to detect each derivative chromosome of a translocation carrier in five couples who requested a prenatal diagnosis in future pregnancies. Most of the human chromoso...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050115
更新日期:1999-01-01 00:00:00