Identification of seven novel CYP11B1 gene mutations in Chinese patients with 11β-hydroxylase deficiency.
Steroid 11β-hydroxylase deficiency (11β-OHD), one of common cause of congenital adrenal hyperplasia (CAH), is an autosomal recessive disorder characterized by virilization, precocious pseudo-puberty, and hypertension. It is caused by CYP11B1 gene mutation. We performed molecular genetic analysis of the CYP11B1 gene in six patients with preliminary clinical diagnosis of 11β-OHD and four patients identified as potential 11β-OHD from a CAH cohort in which CYP21A2 gene mutations consecutively screened. Seven novel CYP11B1 mutations, including p.R454H, p.Q472P, p.Q155X, p.K173X, IVS2-1G>A, R454A fs 573X, and g.2704_g.3154del, and six previously described mutations (p.P94L, p.G267S, p.G379V, p.R448H, p.R454C and p.R141X) were identified. These mutations mainly clustered in exons 3 and 8. Eight of twenty alleles carried mutations occurring at the Arg454 position, which is a mutational hot spot for Han Chinese. The pathogenic nature of novel p.R454H mutation was predicted by protein sequence alignment and in silico analysis. All the identified mutations were responsible for the clinical features observed in these ten unrelated Chinese patients. This study expands the CYP11B1 mutation spectrum and provides evidence for prenatal diagnosis and genetic counseling. Genetic analysis is an alternative approach to help clinicians confirm uncertain 11β-OHD diagnosis, facilitating reasonable steroid replacement.
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: wxjpumch1206@163.com.
Xiaojing
X
Wang
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: nm_pumch@aliyun.com.
Min
M
Nie
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: lulin88@sina.com.
Lin
L
Lu
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: tonganli@hotmail.com.
Anli
A
Tong
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: cs0083@126.com.
Shi
S
Chen
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: luzhaolin39@163.com.
Zhaolin
Z
Lu
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
D013252:Steroid 11-beta-Hydroxylase
11-Beta-hydroxylase deficiency; CYP11B1; Congenital adrenal hyperplasia; Mutation