Isolated p.H62L mutation in the CYP21A2 gene in a simple virilizing 21-hydroxylase deficient patient

TABOAS, M; FERNÁNDEZ C; BELLI S; BUZZALINO N.; ALBA L; DAIN L

CASE REPORTS IN GENETICS

HINDAWI PUBLISHING CORPORATION

Año: 2013 p. 1 - 4

2090-6544

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency accounts for 90?95% of CAH cases. This autosomal recessive disorder, has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilising forms, to the mild late onset or non-classical form. Most of the disease-causing mutations described are likely to be the consequence of non-homologous 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 in disease-causing alleles in the last years. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. To date, thirty-one 21-hydoxylase-deficient patients have been reported carrying the pH62L mutation. It was suggested that the p.H62L represents a mild mutation that may be responsible of a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, it is described a 20-year-old woman carrying an isolated p.H62L mutation in compound heterocygozity with c.283-13A/C>G mutation. Although a mildly non-classical phenotype was expected, clinical signs and hormonal profile of the patient is consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients presenting this mutation would help in defining the role of this variable in disease manifestation.