Mutation analysis of five candidate genes in Chinese patients with hypospadias

Wang, Yanping; Li, Qiang; Xu, Jiajie; Liu, Qingjie; Wang, Weiqiu; Lin, Yi; Ma, Fen; Chen, Taiji; Li, Senkai; Shen, Yan

doi:10.1038/sj.ejhg.5201232

Cited by 101 publications

(118 citation statements)

References 20 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Patient 16 carries the hemizygous p.A620V in MID1 (unpublished data), the heterozygous Q6X and G203S mutations in SRD5A2. 4 Family studies found that, in the patient, the hemizygous p.A620V in MID1 is de novo. In addition, family studies also found that his mother, the carrier of the heterozygous p.P42T in HOXB6 and the heterozygous G203S in SRD5A2, and his father, the carrier of the heterozygous Q6X in SRD5A2, were all healthy.…”

Section: Discussionmentioning

confidence: 90%

“…Some known candidate genes for hypospadias such as SRD5A2, WT1 and AR have already been studied in the 90 patients and some of these patients parents. 4 A total of 190 Chinese normal males with no history of any abnormalities in urogenitory system, limbs and palate, were recruited as a control group. The mean age of the control group was 27 years.…”

Section: Patients and Controlsmentioning

confidence: 99%

“…The mean age of the control group was 27 years. 4 Informed consent was obtained from all patients or their parents. Ethical approval for the study was obtained from the Ethical Committee of the National Center of Human Genome Research, Beijing.…”

Section: Patients and Controlsmentioning

confidence: 99%

“…For example, the inheritance of AR defects, is Xlinked recessive, and SRD5A2 defects autosomal recessive. 4,5 However, all these defects only account for no more than 30% of cases. 6 Thus, the fact that the causes have not yet been identified for a large number of cases highlights the importance of seeking other possible genetic explanations for the congenital defect.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias

Chen

et al. 2006

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

Hypospadias, one of the most common congenital abnormalities of the male external genitalia with elusive etiology, are caused by a defect in the normal development of the urethra, foreskin and ventral aspect of the penis. Evidences indicate that BMP4 and BMP7, two of those major factors in a signaling cascade involved in controlling the embryonic urethral development, play central roles in the normal development of the urethra, and that HOXA4 and HOXB6 play important roles in the development of skin in various tissues at the time course of the urethral development. We directly sequenced all these exons and exonintron boundaries of the four genes in 90 unrelated Chinese patients with hypospadias. Thirteen different heterozygous nucleotide variations were identified for the first time in the four genes in 14 of 90 cases. Of the 13 variations, eight are missense: c.619C4G (p.H207D), c.668G4A (p.R223H), c.751C4T (p.H251Y) in BMP4; c.907C4T (p.R303C) in BMP7; c.385G4T (p.G129C), c.869C4G (p.S290C) in HOXA4; c.124C4A (p.P42T), c.367T4C (p.C123R) in HOXB6. None of these variations were found in 380 control chromosomes. Amino-acid sequence alignments showed most of these changed amino acids are conserved across various vertebrate species. In a word, these findings, together with the indicated roles of the four genes, imply that it should not be random events for so many nucleotide variations found in the present study. Further functional studies are required to make the associations clear between these variants and hypospadias.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Patients and Controlsmentioning

confidence: 99%

Section: Patients and Controlsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias

Chen

et al. 2006

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous findings could not be generalised to a Chinese population in our study. Large Chinese sample sizes for MAMLD1 in Chinese populations are currently absent (18), and the frequency of MAMLD1 mutations in a larger sample from a Chinese population should be investigated.…”

Section: Discussionmentioning

confidence: 99%

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

Zhuang¹,

Bai²,

Zhou³

et al. 2014

Journal of Medical Biochemistry

View full text Add to dashboard Cite

Summary Background: This study aimed to investigate the significance of MAMLD1 mutations in the incidence of hypospa-dias in a Chinese population. Methods: The experimental group consisted of 150 domestic children with hypospadias, aged 0.5 to six years and living in different provinces. A total of 120 normal children, aged two to six years, served as the control group. DNA was extracted for the direct sequencing of MAMLD1 genes. Results: Twelve cases (8.0%) of the missense mutation p.N589S were found in the experimental group, whereas four cases (3.0%) of the same mutation were found in the control group. No significant difference was observed in the mutation rate between the two groups (P>0.05). Four cases (2.7%) had a new missense mutation p.P567S in the experimental group, and three cases (2.5%) possessed the same mutation in the control group. No significant difference was observed between the two groups (P>0.05). Conclusions: In this study, the importance of repeated experiments in mutation-related studies was confirmed, which revealed the difference in predisposing genes among different populations. Although the mutation of the MAMLD1 gene had no apparent connection with the incidence of hypospadias in a Chinese population, a new mutation site of the MAMLD1 gene was discovered, which could provide new research topics for future studies.

show abstract

Vertical transmission of a mutation in exon 1 of the WT1 gene: Lessons for genetic counseling

Regev

Kirk

Mashevich

et al. 2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We present a vertical transmission of a nonsense mutation in exon 1 of the Wilms' tumor WT1 gene, from a mother who had Wilms' tumor in infancy and decreased fertility at adulthood, to her son who displayed genitourinary (GU) anomalies, gonadal dysgenesis with gonadoblastoma foci, and intra-abdominal Mullerian derivatives. No Wilms' tumor was detected up to the age of 6 years in the son. Sequence analysis of constitutional DNA of the WT1 gene revealed a heterozygous c.327C > A sequence change in exon 1 leading to a premature stop codon at amino acid 109. This mutation demonstrates the lack of correlation between genotype-phenotype and mutation position in the WT1 gene, the presence of intra-familial variability, and the effect of gender on severity of GU anomalies. We suggest that detection of a GU defect in the presence of parental history of Wilms' tumor be followed up by screening of constitutional DNA for WT1 mutations. Explorative laparoscopy for sex organ evaluation and gonadal assessment for possible gonadoblastoma should be considered when constitutional mutation is detected in males with GU anomalies.

show abstract

Mutation analysis of five candidate genes in Chinese patients with hypospadias

Cited by 101 publications

References 20 publications

Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias

Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

Vertical transmission of a mutation in exon 1 of the WT1 gene: Lessons for genetic counseling

Contact Info

Product

Resources

About