Hindawi Publishing Corporation Case Reports in Genetics Volume 2013, Article ID 143781, 4 pages http://dx.doi.org/10.1155/2013/143781 Case Report Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient Melisa Taboas, 1,2 Cecilia Fernández, 1 Susana Belli, 3 Noemi Buzzalino, 1 Liliana Alba, 1 and Liliana Dain 1,2 1 Centro Nacional de Gen` etica M´ edica, ANLIS “Dr. Carlos G. Malbr´ an”, Buenos Aires, Argentina 2 Instituto de Biolog` ıa y Medicina Experimetal, CONICET, Buenos Aires, Argentina 3 Divisi` on Endocrinolog´ ıa, Hospital Durand, Buenos Aires, Argentina Correspondence should be addressed to Liliana Dain; ldain@fmc.fcen.uba.ar Received 13 May 2013; Accepted 15 June 2013 Academic Editors: M. Fenger, S. F. Grant, and G. Vogt Copyright © 2013 Melisa Taboas et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Congenital adrenal hyperplasia due to 21-hydroxylase defciency accounts for 90%–95% of cases. Tis autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. Te change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profle of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase defciency. Te study of genotype-phenotype correlation in additional patients would help in defning the role of p.H62L in disease manifestation. 1. Introduction Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase defciency (OMIM 201910) accounts for 90%–95% of CAH cases [1, 2]. Tis autosomal recessive disorder, which is the most frequent inborn error of metabolism, has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting (SW) and simple virilizing (SV) forms, to the mild late onset or nonclassical form of CAH (NCCAH) [1]. Te afected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Due to the high degree of identity between this gene and its pseudogene, most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events [3, 4]. In addition, more than 130 rare point mutations that arise independently of the pseudogene and that were found specifc to a pop- ulation or a single family, have been described to date (for details visit http://www.hgmd.cf.ac.uk). Most of the patients are compound heterozygotes and their phenotype depends on the underlying combination of mutations they have [5]. Te change p.H62L is one of the most frequent rare muta- tions of the CYP21A2 gene. Based on patients’ phenotypes and functional studies, it has been proposed that the p.H62L allele represents a mild mutation, which may be responsible for a more severe phenotype only when associated with another mild mutation on the same allele [6, 7]. Moreover, by in silico analyses using as a template the crystallized bovine CYP21 that shares 79% sequence identity with the human CYP21A2 protein, Haider et al. (2013) associate this mutation to the mild form of the disease [8]. Herein we describe a recently genotyped patient from our cohort carrying an isolated p.H62L mutation in one allele and the severe c.283-13A/C>G mutation in the other