Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%–95% of cases. This 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. The 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 profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation. 1. Introduction Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (OMIM 201910) accounts for 90%–95% of CAH cases [1, 2]. This 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]. The affected 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 specific to a population 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]. The change p.H62L is one of the most frequent rare mutations of the
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