A complex heterozygous mutation of His373Leu and Asp487-Ser488-Phe489 deletion in human cytochrome P450c17 causes 17alpha-hydroxylase/17,20-lyase deficiency in three Chinese sisters.
Cytochrome P450c17 deficiency is one of the rare forms of enzyme disorders in steroid biosynthesis, resulting from defects in 17alpha-hydroxylase and 17,20-lyase activities. The disease is caused by the mutations in CYP17 gene, inherited in an autosomal recessive pattern. We reported a Chinese family with three sisters suffering from P450c17 deficiency based on their clinical features and molecular genetics. The patients were found to be compound heterozygotes with two different mutations. Screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), a heterozygous point mutation His373Leu was detected in the exon 6 of CYP17 gene which was proved to be derived from paternal allele. The other allele contained nine-base pair deletion, located in exon 8, eliminating codons 487-489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. The mother and the brother have been demonstrated to be carriers of deletion mutation through restriction enzyme analysis. Both mutations have been reported previously in Asia. This is the first report of the molecular genetic study of 17alpha-hydroxylase/17,20-lyase deficiency in mainland China with a novel compound heterozygous mutation.
Qiao
Jie
J
Ruijin Hospital, Shanghai Institute of Endocrinology, Shanghai Second Medical University, 197 Ruijin Road II, People's Republic of China.
Hu
Ren-Ming
RM
Peng
Yong-De
YD
Song
Huai-Dong
HD
Peng
Yi-Wen
YW
Gao
Guo-Feng
GF
Hao
Jian-Hua
JH
Hu
Nan-Ying
NY
Xu
Man-Yin
MY
Chen
Jia-Lun
JL
D000328:Adult; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015183:Restriction Mapping; D017384:Sequence Deletion; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism
D013254:Steroid 17-alpha-Hydroxylase