Mutation Spectrum of STAR and the Founder Effect of p.Q258* in Korean Patients with Congenital Lipoid Adrenal Hyperplasia

Eungu Kang, Yoon-Myung Kim, Gu-Hwan Kim, Beom Hee Lee, Han-Wook Yoo, and Jin-Ho Choi
Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia, caused by defects in the steroidogenic acute regulatory protein (STAR). The STAR p.Q258* mutation is the most common mutation in China, Japan and Korea, suggesting a founder effect. This study aimed to investigate the phenotypic and mutation spectrum of STAR defects and identify the founder effect of the p.Q258* mutation in Korean patients with CLAH. For 45 patients from 42 independent pedigrees, haplotype analysis was performed in 10 unrelated trio families, including patients with the p.Q258* mutation whose DNA samples were available, using 1,972 single nucleotide polymorphism (SNP) and six short tandem repeat markers. An Illumina Infinium® Human Omni2.5-8 v1.3 performed the SNP genotyping. Among 84 alleles from 42 unrelated families, mutation p.Q258* was found in 74 alleles (88.1%) from 41 families. A shared haplotype was identified in 17 of 20 alleles from 10 patients (size, 198 kb). The age of the founder mutation was estimated as 4,875 years (95% credible set: 3,575–7,925 years), assuming an intergenerational time interval of 25 years. The STAR p.Q258* mutation is the most common in Korean patients with CLAH, suggesting a founder effect.The age of the mutation corresponds with the time when the Korean people settled in the Korean peninsula. The high prevalence of p.Q258* in Japan and China also suggests a founder effect in Asian countries.
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Date Published
May 2, 2017
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Kang, Kim, Lee, Yoo, Choi, congenital lipoid adrenal hyperplasia, CLAH, steroidogenic acute regulatory protein, STAR, STAR p.Q258* mutation, adrenal steroid hormones, mitochondrial membrane, STAR gene, genetic markers
Article Type
Research Article