Congenital adrenal hyperplasia (CAH) is one of the inborn metabolic disorders inherited in an autosomal recessive manner. 95% of CAH cases are due to 21-hydroxylase deficiency. 21-hydroxylase enzyme have an active gene and a pseudogene. The rearrangements between these two genes play an important role in the pathogenesis of CAH. Herein, we present the cases of two siblings with different phenotypes and different chromosomal sex who both have a large gene conversion and a point mutation.
21-hydroxylase gene strip assay and MLPA analysis were performed in the two sibling cases.
The case with male phenotype has been diagnosed with CAH due to salt-wasting crises, macrogenitalia, and hyperpigmentation when he was 1 month old. Karyotype analysis results were 46,XY and SRY(+). The female case with 46,XX has been diagnosed with CAH due to salt-wasting crises and ambiguous genitalia in the newborn period. Results of CAH strip assays were c.89C>T(P30L) (N/M), c.329-336del(Del 8bp E3) (N/M), c.290-13A/C>G (I2 Splice) (M/M) in both cases. In MLPA analysis, heterozygous increase in CYP21A1P-1 (-113 SNP) and CYP21A1-P-3 (del8nt) mutation regions, heterozygous loss in CYP21A2-1wt (-113 SNP) and CYP21A2-3 wt (del8nt) regions, and homozygous mutations in CYP21A2-3 wt (I2 G-C), CYP21A2-3 wt (I2G-A) regions were detected. It was thought that the cases have received an allele with heterozygous mutation in c.290-13A/C>G (I2 Splice) region from one parent and a gene converted allele from the other. Mutation analysis was planned for parents.
The cases were presented here in order to emphasize the importance of MLPA analysis when diagnosing CAH.