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Phenotype and molecular characteristics in 45 Chinese children with 5α‐reductase type 2 deficiency from South China
Author(s) -
Cheng Jing,
Lin Ruizhu,
Zhang Wen,
Liu Guochang,
Sheng Huiying,
Li Xiuzhen,
Zhou Zhihong,
Mao Xiaojian,
Liu Li
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12799
Subject(s) - compound heterozygosity , phenotype , genotype , context (archaeology) , genotype phenotype distinction , genetics , medicine , endocrinology , gene , mutation , hypospadias , biology , microbiology and biotechnology , paleontology
Summary Context Affected by steroid 5α‐reductase type 2 deficiency (5α‐ RD 2), 46, XY individuals present divergent phenotypes characterized by undervirilization of male external genitalia. To identify the disorder, mutational analysis of 5α‐reductase type 2 gene ( SRD 5A2) is a reliable approach. The genotype–phenotype relationship has not been elucidated. Objective To improve the diagnosis and expand the knowledge of the disease, we collected and analysed relevant data of clinical diagnosis, biological investigation and molecular determination in 45 children with the SRD 5 A 2 gene mutations from S outh C hina in our centre. Subjects and methods We studied a cohort of 45 C hinese children with SRD 5 A 2 gene mutations. Results Isolated microphallus (35·6%) and microphallus associated with various degrees of hypospadias (55·6%) were frequent phenotype. Female external genitalia with clitoromegaly (8·9%) were rare. 16 of 18 (88·9%) cases had hCG ‐stimulated T / DHT ratio above 10. In 45 patients, we identified 15 different mutations. Five have never been described: p. H is90 T hrfs X 31, p. G ly21 A rg, p. G ly149 A sp, p. A rg145 L eu and p. G ly66 A rg. The p. A rg227 G ln mutation was detected in 41 (91·1%) patients. The p. L eu89 V al polymorphism was found in 38 (84·4%) patients. Homozygous mutations were presented in 16 (35·6%) patients, compound heterozygous mutations in 20 (44·4%) patients, compound heterozygous mutations alone with the p. L eu89 V al polymorphism in nine (20·0%) patients. Exons 1 and 4 were most affected, and the number of mutant alleles per exon was 78·1% and 12·2%, respectively. Conclusions The study demonstrated a wide spectrum of phenotypes, biological profiles and genotypes in the children with 5α‐ RD 2 from S outh C hina. The heterozygous mutation p. A rg227 G ln is presumably a hot spot mutation and suggests a founder effect in the population of S outh C hina that may explain a moderate phenotype among our patients. Our report provides new insights into the molecular mechanism of 5α‐ RD 2 and help to the diagnosis and treatment of this disease.