Molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Hong Kong Chinese patients
| Autor: | P.Y. Loung, C.W. Cheng, W.Y. Tse, L.M. Wong, Y.Y. Lam, S.C. Tiu, Angel O.K. Chan, K.L. Ng, C.Y. Lee, W.M. But, Ruth Charlton, K.F. Lee, Ian R. Berry, C.C. Shek, Rebecca Brown, Y.C. Ho |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Genotype Clinical Biochemistry Mutant Biochemistry Endocrinology Congenital adrenal hyperplasia due to 21-hydroxylase deficiency Asian People medicine Humans Congenital adrenal hyperplasia Multiplex ligation-dependent probe amplification Allele Molecular Biology Genotyping Alleles Pharmacology Genetics Adrenal Hyperplasia Congenital business.industry Point mutation Organic Chemistry Infant medicine.disease Child Preschool Mutation Hong Kong Female Steroid 21-Hydroxylase business |
| Zdroj: | Steroids. 76:1057-1062 |
| ISSN: | 0039-128X |
| DOI: | 10.1016/j.steroids.2011.04.010 |
| Popis: | Background Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder due to mutation in the CYP21A2 gene. Objective To elucidate the genetic basis of 21-hydroxylase-deficient CAH in Hong Kong Chinese patients. Patients and methods Mutational analysis of the CYP21A2 gene was performed on 35 Hong Kong Chinese patients with 21OHD using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Results The genetic findings of 21 male and 14 female patients are the following: c.293-13A/C>G (intron 2 splice site; 20 alleles), p.I172N (13), p.R356W (7), p.Q318X (4). A total of 20 mutant alleles contained gross deletion/conversion of all or part of the CYP21A2 gene. A novel mutation, c.1367delA (p.D456fs), was detected in one patient. One patient had only a heterozygous mutation detected. Out of 35 patients, 16 would have been incorrectly genotyped if either DNA sequencing or MLPA alone was used for molecular analysis. Conclusions The frequency of various mutations in the studied patients differs from those reported in other Asian populations. Gross deletion/conversion accounts for nearly one-third of the genetic defects. Therefore, laboratories must include methods for detecting point mutations as well as gross deletions/conversions to avoid misinterpretation of genotype. Genotyping has increasingly been proven to be a useful tool for supplementing, if not replacing, hormonal profiling for the diagnosis of 21OHD. |
| Databáze: | OpenAIRE |
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