Molecular diagnosis of two families with classic congenital adrenal hyperplasia

We investigated the genetic defects in two families with classic congenital adrenal hyperplasia (CAH). Clinical data and vein blood of the family members were collected, hormonal evaluation, karyotype analysis, ultrasound and CT scans were performed, and a direct-sequencing of PCR products of the candidate genes was used to identify the mutations. In family A, Patients A-II:1 and A-II:2 were found to be in a compound heterozygous state for mutations of p.I172N (g.1004 T > A) in exon 4 and IVS2-13A/C > G (g.659A/C > G) in intron 2 in CYP21A2 gene, their father A-I:1 and mother A-I:2 were found to carry a heterozygous mutation of IVS2-13A/C > G (g.659A/C > G) and p.I172N (g.1004 T > A) respectively. In family B, Patient B-II:1 was detected to carry only one heterozygous mutation of p.I172N; no other mutations in CYP11B1, CYP17A1 or HSD3B2 genes were detected. Her father B-I:1 carried a heterozygous mutation of p.I172N (g.1004 T > A) and her mother B-I:2 was found to be a wild type in all the candidate genes. Obviously, patients A-II:1 and A-II:2 inherited the p.I172N (g.1004 T > A)-bearing maternal allele and the IVS2-13A/C > G (g.659A/C > G)-bearing paternal allele. And this kind of compound heterozygous mutations caused simple virilising (SV) CAH. While patient B-II:1, whose phenotype was SV CAH too, was found to carry only one heterozygous mutation of the p.I172N (g.1004 T > A)-bearing paternal allele, and needed further studies.