A Novel Nonsense Mutation c.374C>G in CYP21A2 Gene of a Vietnamese Patient with Congenital Adrenal Hyperplasia
Inactivating mutations of the CYP21A2 gene, encoding for steroid synthesis, have been reported in patients with congenital adrenal hyperplasia (CAH). We report a case of an infant who were diagnosed with CAH and presented with the severe phenotype of CAH
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A Novel Nonsense Mutation c.374C>G in CYP21A2 Gene of a Vietnamese Patient with Congenital Adrenal Hyperplasia Chi Dung Vu, Thanh Van Ta, Ngoc-Lan Nguyen, HuyHoang Nguyen, Thi Kim Lien Nguyen, Thinh Huy Tran, and Van Khanh Tran Abstract
Inactivating mutations of the CYP21A2 gene, encoding for steroid synthesis, have been reported in patients with congenital adrenal hyperplasia (CAH). We report a case of an infant who were diagnosed with CAH and presented with the severe phenotype of CAH with symptoms such as increased testicular volume, elevated of 17-hydroxyprogesteron, testosterone and progesterone. In this study, we established an assay for the detection of unusual genetic in the CYP21A2 gene in the proband and his family. A novel nonsense mutation c.374C > G which caused a substitutions of
Authors Chi Dung Vu and Thanh Van Ta have been equally contributed to this chapter. C. D. Vu Center for Gene and Protein Research, Hanoi Medical University, Hanoi, Vietnam Vietnam National Children Hospital Hanoi, Vietnam, Department of Medical Genetics, Metabolism & Endocrinology, Hanoi, Vietnam T. Van Ta (*), T. H. Tran, and V. K. Tran Center for Gene and Protein Research, Hanoi Medical University, Hanoi, Vietnam e-mail: [email protected] N.-L. Nguyen, H.-H. Nguyen, and T. K. L. Nguyen Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
Serine for a stop codon at codon 125 (p.S125*) within exon 3 was found in the proband. Parental genotype studies confirmed carrier state in the father, but the mother showed a wild allele by PCR and sequencing. This inspired us to find deletions using multiplex ligation-dependent probe amplification (MLPA) technique. The probands were found to have a large deletion in exons 1 and 3, while the mother only had deletion in exon 1. Therefore, mutation c.374C > G (p.S125*) in the proband is considered as a heterozygous deletion. This mutation caused a truncated protein which lead to the salt wasting CAH phenotype of the proband. This novel nonsense mutation expands the CYP21A2 mutation spectrum in CAH disorder. This case also highlights the need of caution when interpreting results of molecular genetic testing during genetic counseling. Keywords
Congenital adrenal hyperplasia (CAH) · CYP12A2 gene · Nonsense mutation · p.S125*
Abbreviations 17-OHP CAH
17-hydroxyprogesterone Congenital adrenal hyperplasia
C. D. Vu et al.
MLPA NC SV SW WT
1
Multiplex ligation-dependent probe amplification Nonclassical CAH Simple virilizing CAH Salt-wasting CAH Wild-type
Introduction
Congenital adrenal hyperplasia (CAH; OMIM6¼ 201910) is a group of autosomal recessive disorders affecting the steroid synthesis pathway, clinically characterized by the occurrence of salt wasting, dehydration, and simple virilization in both sexes and ambiguous genitalia in the female (White and Speiser 2000; Speiser et al. 2010; Haider et al. 2013). In Vietnam, CAH occurs with an estimated prevalence of 1 in 100,000. CAH is caused by mutations in the CYP21A2 gene. CYP21A2 gene encoding 21
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