Abstract:
:Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Lee BH,Kim GH,Oh TJ,Kim JH,Lee JJ,Choi SH,Lee JY,Kim JM,Choi IH,Kim YM,Choi JH,Yoo HWdoi
10.1038/jhg.2013.67subject
Has Abstractpub_date
2013-09-01 00:00:00pages
604-10issue
9eissn
1434-5161issn
1435-232Xpii
jhg201367journal_volume
58pub_type
杂志文章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::Ectodermal-dysplasia-syndactyly syndrome (EDSS1) is a rare form of ectodermal dysplasia (ED), affecting skin and its appendages mainly hair, teeth and nails. In the present study, we have investigated a large consanguineous Pakistani family with 10 individuals showing features of EDSS1. Human genome was screened using...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.18
更新日期:2011-05-01 00:00:00
abstract::We constructed a high-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the DiGeorge syndrome critical region 2 (DGCR2) gene at chromosome 22q11.2, a human counterpart of mouse seizure-related gene SEZ-12. A total of 102 SNPs were isolated from the region by systematic screening among 48 ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170029
更新日期:2001-01-01 00:00:00
abstract::We determined the genomic structure of the human gene encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate and is the rate-limiting and major regulatory enzyme in sterol biosynthesis. The gene is more than 21 kb long, about five times the size of i...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070017
更新日期:2000-01-01 00:00:00
abstract::Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study. The most common...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.136
更新日期:2014-03-01 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::We found a five-basepair insertion/deletion polymorphism in intron 3 of TNNT2, one of the genes responsible for hypertrophic cardiomyopathy. These five bases may be part of an intronic polypyrimidine tract sequence that may affect splicing. The purpose of the study was to examine the association of the polymorphism wi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0121-4
更新日期:2004-01-01 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::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::Pericentric inversions are among the known polymorphisms detected in the general population at a frequency of 1-2%. Despite their generally benign nature, pericentric inversions affect the reproductive potential of carriers by increasing the risk for unbalanced live-born offspring, miscarriages, or other fertility pro...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0769-z
更新日期:2020-09-01 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::Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0263-7
更新日期:2005-01-01 00:00:00
abstract::Although many studies have been performed to identify mutations in Korean patients with various autosomal-recessive Mendelian disorders (AR-MDs), little is known about the carrier frequencies of AR-MDs in the Korean population. Twenty common mutations from six AR-MDs, including Wilson disease (WD), non-syndromic heari...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.144
更新日期:2012-02-01 00:00:00
abstract::In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recomb...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.46
更新日期:2016-08-01 00:00:00
abstract::Mutations in CDH1, which encodes E-cadherin, have been associated with hereditary diffuse gastric cancer (HDGC) in Western populations but have not been shown to play a major role in Asians. Recently, a patient with familial gastric cancer (FGC) was shown to harbor a germline mutation in the TP53 gene, which encodes p...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0193-9
更新日期:2004-01-01 00:00:00
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 ha...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-021-00904-2
更新日期:2021-01-27 00:00:00
abstract::ORAI1 encodes a calcium channel essential in the store-operated calcium entry mechanism. A previous genetic association study identified a rare in-frame insertion variant of ORAI1 conferring Kawasaki disease (KD). To deepen our understanding of the involvement of rare variants of ORAI1 in KD pathogenesis, we investiga...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0588-2
更新日期:2019-06-01 00:00:00
abstract::Hypohidrotic ectodermal dysplasia (HED) is characterized by severe hypohidrosis, hypotrichosis, and hypodontia. It can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns. Mutations in the EDA gene, which encodes ectodysplasin-A, are responsible for X-linked HED (XLHED). In the present study,...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0071-8
更新日期:2006-01-01 00:00:00
abstract::CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signa...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/s10038-017-0376-9
更新日期:2018-02-01 00:00:00
abstract::Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase ( MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggeste...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200043
更新日期:2002-01-01 00:00:00
abstract::Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease with autosomal dominant transmission characterized by the presence of malformations of the big toes and of postnatal progressive heterotopic endochondral osteogenesis. We report the case of 3-year-old girl with dysplasia of the first metatarsal b...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0069-2
更新日期:2006-01-01 00:00:00
abstract::We report the clinical and biochemical findings from a patient who presented with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal-dominant disorder characterized by optic atrophy, developmental delay and intellectual disability. In addition, the patient also displays hypotonia, stroke-like episodes...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-017-0398-3
更新日期:2018-04-01 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::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::Premature ovarian failure (POF) is a disorder characterized by amenorrhea and elevated serum gonadotropins before 40 years of age. As X chromosomal abnormalities are often recognized in POF patients, defects of X-linked gene may contribute to POF. Four cases of POF with t(X;autosome) were genetically analyzed. All the...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.155
更新日期:2011-02-01 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::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::The differential transmission of alleles from parents to affected children indicates that the locus under investigation is either directly involved in the occurrence of the disease or that there are allelic associations with other loci that are directly involved. Conditional logistic regression applied to a diallelic ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0217-5
更新日期:2005-01-01 00:00:00
abstract::Spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders with almost 30 subtypes. The prevalence and relative frequency of each subtype vary among different populations. In this article, we report the relative frequency of six SCA subtypes in the Thai population and attempt to explain the observed pattern...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.27
更新日期:2009-05-01 00:00:00
abstract::Erythropoietic protoporphyria (EPP) is an inherited disorder, caused by a partial deficiency of ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway. The deficiency results in accumulation of protoporphyrin, primarily in erythroid cells, and the major clinical feature is cutaneous photosensitivity. ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380300009
更新日期:2003-01-01 00:00:00