PTPN11 , SOS1 , KRAS , and RAF1 gene analysis, and genotype–phenotype correlation in Korean patients with Noonan syndrome
Abstract
After 2006, germline mutations in the KRAS, SOS1, and RAF1 genes were reported to cause Noonan syndrome (NS), in addition to the PTPN11 gene, and now we can find the etiology of disease in approximately 60–70% of NS cases. The aim of this study was to assess the correlation between phenotype and genotype by molecular analysis of the PTPN11, SOS1, KRAS, and RAF1 genes in 59 Korean patients with NS. We found disease-causing mutations in 30 (50.8%) patients, which were located in the PTPN11 (27.1%), SOS1 (16.9%), KRAS (1.7%), and RAF1 (5.1%) genes. Three novel mutations (T59A in PTPN11, K170E in...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Genetic variants of FOXA2: risk of type 2 diabetes and effect on metabolic traits in North Indians
Abstract
Here, we examined the association of genetic variants of FOXA2, an upstream activator of the β-cell transcription factor network, with type 2 diabetes and related phenotypes in North India. We genotyped three SNPs (rs1212275, rs1055080, rs6048205) and the (TCC)
n
repeat polymorphism in 1,656 participants comprising 1,031 patients with type 2 diabetes and 625 controls. SNPs rs1212275 and rs6048205 were uncommon (MAF < 5%) with similar distribution among patients and controls. We found a strong association of (TCC)
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...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects
Abstract
Genetic variants of the transcription factor 7-like 2 (TCF7L2) gene affect the risk of type 2 diabetes in populations with multiple ethnic groups. However, a comprehensive survey of this gene has not been done for a Japanese population. Thus, we conducted this gene-based association study, in which the common genetic variants were analyzed. Using 24 Japanese type 2 diabetic subjects, we first screened a 9.5 kb region, which included the entire coding sequence, to assess potential functional variants of TCF7L2. Sequencing revealed a common coding variant (Pro477Thr) in exon 14 of TCF7L2 that wa...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Association study to evaluate the serotonin transporter and apolipoprotein E genes in frontotemporal lobar degeneration in Italy
Abstract
Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder characterized by behavioral and language disturbances. We performed a case-control association study in the Italian population to assess the relevance for FTLD genetic susceptibility of the serotonin (5-HT) transporter gene-linked polymorphic region [rs4795541, alias short (S)/long (L)] an in/del polymorphism of the promoter region of the gene coding for the 5-HT transporter (SLC6A4). This functional polymorphism was reported to influence the SLC6A4 transcription rate, with the S-allele having a two-fold reduce...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific
In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI*A was divided into two suballeles, CFI*As (R201S) and CFI*Ah (R406H). CFI*Aj, a rare variant allele originating from CFI*Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI*As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population
In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to disease
Abstract
Marfan syndrome (MFS) results from heterozygous mutations in FBN1. However, genetic analyses of deoxyribonucleic acid (DNA) from approximately 10–30% of MFS patients who meet diagnostic criteria do not reveal an identifiable FBN1 mutation. In a patient who met the diagnostic criteria for MFS, bidirectional DNA sequencing of exons and intron–exon boundaries of FBN1 failed to reveal a mutation. Assessment of the FBN1 message in dermal fibroblasts from the patient revealed insertion of a pseudoexon between exons 63 and 64. Sequencing of intron 63 identified a point mutation, IVS63+373, located...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype–phenotype correlation in Korean patients with Noonan syndrome
Abstract
After 2006, germline mutations in the KRAS, SOS1, and RAF1 genes were reported to cause Noonan syndrome (NS), in addition to the PTPN11 gene, and now we can find the etiology of disease in approximately 60–70% of NS cases. The aim of this study was to assess the correlation between phenotype and genotype by molecular analysis of the PTPN11, SOS1, KRAS, and RAF1 genes in 59 Korean patients with NS. We found disease-causing mutations in 30 (50.8%) patients, which were located in the PTPN11 (27.1%), SOS1 (16.9%), KRAS (1.7%), and RAF1 (5.1%) genes. Three novel mutations (T59A in PTPN11, K170E in...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
LRRK2 P755L variant in sporadic Parkinson’s disease
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder of unknown etiology with probable involvement of genetic-environmental factors. The majority of PD cases (approximately 90–95%) are sporadic, while familial cases account for approximately 5–10% of PD. In a recent report, a heterozygous LRRK2 P755L mutation within LRRK2 exon 19 was found in 2% of Chinese sporadic PD patients and in 0% of normal controls or Caucasians, suggesting that the mutation is disease-associated with ethnic specificity. To further evaluate the role of LRRK2 P755L variant in sporadic PD, we performed direct seq...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Nonparametric estimation of LOH using Affymetrix SNP genotyping arrays for unpaired samples
Abstract
Studies of loss of heterozygosity (LOH) play an important role in cancer research. In this paper, we developed a two-step procedure to examine LOH by comparing unpaired tumour and normal samples. In the first step we determined which chromosomes significantly differ between the two sets of samples by using nonparametric procedures. We then used the biplot data visualisation technique and homozygosity intensity estimates to determine the regions of these chromosomes that required further examination. We illustrated our method by examining 22 autosomes in samples of 95 normal controls and 14 acut...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Association of the SLC45A2 gene with physiological human hair colour variation
Abstract
Pigmentation is a complex physical trait with multiple genes involved. Several genes have already been associated with natural differences in human pigmentation. The SLC45A2 gene encoding a transporter protein involved in melanin synthesis is considered to be one of the most important genes affecting human pigmentation. Here we present results of an association study conducted on a population of European origin, where the relationship between two non-synonymous polymorphisms in the SLC45A2 gene — rs26722 (E272K) and rs16891982 (L374F) — and different pigmentation traits was examined. The st...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population
Abstract
Mutations in the GJB2 gene are associated with hereditary hearing loss. Although most studies of GJB2 mutations have dealt with hearing-impaired patients, there are few reports of the frequency of these mutations in the general population. The purpose of this study is to evaluate the prevalence of GJB2 mutations causing inherited deafness in the general Korean population. Blood samples were obtained from 2,072 newborns with normal hearing. The dried blood samples were subjected to PCR to amplify the entire coding region of the GJB2 gene, which was followed by direct DNA sequencing. A total of 2...
Source: Journal of Human Genetics - December 1, 2008 Category: Genetics & Stem Cells Source Type: research
PTPN11 , SOS1 , KRAS , and RAF1 gene analysis, and genotype –phenotype correlation in Korean patients with Noonan syndrome
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > After 2006, germline mutations in the < em class= " a-plus-plus " > KRAS < /em > , < em class= " a-plus-plus " > SOS1 < /em > , and < em class= " a-plus-plus " > RAF1 < /em > genes were reported to cause Noonan syndrome (NS), in addition to the < em class= " a-plus-plus " > PTPN11 < /em > gene, and now we can find the etiology of disease in approximately 60 –70% of NS cases. The aim of this study was to assess the correlation between phenotype and genotype by molecular analysis of the < em class= " a-plus-plus " > PTPN11 < /em > , < em class= "...
Source: Journal of Human Genetics - November 30, 2008 Category: Genetics & Stem Cells Source Type: research
LRRK2 P755L variant in sporadic Parkinson ’s disease
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Parkinson ’s disease (PD) is a neurodegenerative disorder of unknown etiology with probable involvement of genetic-environmental factors. The majority of PD cases (approximately 90–95%) are sporadic, while familial cases account for approximately 5–10% of PD. In a recent report, a heterozygous < em class= " a-plus-plus " > LRRK2 < /em > P755L mutation within < em class= " a-plus-plus " > LRRK2 < /em > exon 19 was found in 2% of Chinese sporadic PD patients and in 0% of normal controls or Caucasians, suggesting that the mutation is disease-a...
Source: Journal of Human Genetics - November 30, 2008 Category: Genetics & Stem Cells Source Type: research
Monozygotic female twins discordant for Silver –Russell syndrome and hypomethylation of the H19-DMR
AbstractSilver –Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and is frequently caused by hypomethylation of the paternally derivedH19-DMR (epimutation). We observed 5 8/12-year-old female twins discordant for SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and bilateral fifth finger clinodactyly, whereas the other twin showed apparently normal phenotype. Microsatellite analysis for 26 loci on multiple chromosomes showed monozygosity. Methylation analysis for theH19-DMR indicated e...
Source: Journal of Human Genetics - October 1, 2008 Category: Genetics & Stem Cells Source Type: research
