[Identification of mutations of SRD5A2 gene and SRY gene in patients with hypospadias].
OBJECTIVE
To identify possible molecular mechanism underlined hypospadias and any relationship of the mutations of SRD5A2 gene and SRY gene to hypospadias.


METHODS
Twenty-three blood samples from the patients with hypospadias were obtained from Aug.1996 to Jan. 1998. DNA was extracted from blood leukocytes. Exons 1 to 5 of the SRD5A2 gene and exon of the SRY gene were amplified by PCR. Mutation detection was performed using PCR-SSCP/silver staining and direct DNA sequencing.


RESULTS
In 3 cases (named 5R2-China-1, 5R2-China-2, and 5R2-China-3), DNA sequencing revealed that a homozygous change from nucleotide G to A occurred in 5R2-China-1 and 2, leading to a substitution of glutamine to arginine in the codon 227(Arg 227 to Gln). In the third patient (5R2-China-3), DNA sequencing revealed two different heterozygous mutations(Arg 227 to Gln, Phe 186 to Leu) in exon 4 of the SRD5A2 gene. No mutation of SRY gene was found in all patients.


CONCLUSIONS
The mutation of SRD5A2 gene affects the differentiation of the external genitalia and may play a role in the etiology of hypospadias. Since no mutation of SRY gene was found, this study might suggest that the mutation of SRY gene is not an important event in hypospadias. Codon 227 is a hotspot site of mutation within the gene. The mutation of codon 186(Phe 186Leu) represents a new form of SRD5A2 mutation.
Zhou
L
L
Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-Sen University of Medical Sciences, Guangzhou, Guangdong, 510080 P.R.China. Lizhou@Gzsums.edu.cn
Mei
H
H
Liu
T
T
Guang
W
W
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007021:Hypospadias / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase