Novel CYP17A1 mutation in a Japanese patient with combined 17a-hydroxylase/17,20-lyase deficiency

作者：Katsumata Noriyuki^*; Ogawa Eishin; Fujiwara Ikuma; Fujikura Kaori

来源：Metabolism-Clinical and Experimental, 2010, 59(2): 275-278.

DOI：10.1016/j.metabol.2009.07.024

Combined 17 alpha-hydroxylase/17.20-lyase deficiency is caused by a defect of P450c17 that catalyzes both 17 alpha-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads In the present study. we analyzed the CYP17A1 gene in a Japanese girl with 17 alpha-hydroxylase/17,20-lyase deficiency The patient was referred to us for clitoromegaly at the age of 3 years The karyotype was 46,XY The patient was diagnosed as having 17a-hydroxylase/17,20-Iyase deficiency based on the clinical and laboratory findings Analysis of the CYP17A1 gene revealed a compound heterozygous mutation One mutation was a deletion of codon 53 or 54 encoding Phe (TTC) in exon 1 (Delta F54) on a maternal allele, which has been previously shown to partially abolish both 17 alpha-hydroxylase and 17,20-Iyase activities The other was a novel missense mutation resulting in a substitution of Asn (AAC) for His (CAC) at codon 373 in exon 6 (H373N) on a paternal allele Functional expression study demonstrated that the H373N mutation almost completely eliminates enzymatic activity Previous studies have demonstrated that replacement of histidine by leucine at position 373 causes complete loss of both 17a-hydroxylase and 17,20-lyase activities with a defect in heme binding due to a global alteration of P450c17 structure, indicating the importance of H373 for P450c17 structure and function Together, these results indicate that the patient is a compound heterozygote for the AI:54 and H383N mutations and that these m

• 出版日期2010-2