[Analysis of CYP21A2 gene mutations in two families with 21-hydroxylase deficiency].

[congenital adrenal hyperplasia]

To analyze CYP 21 A 2 gene mutation in two families with 21 -hydroxylase deficiency (21 -OHD ) and to explore the correlation between genotype and clinical phenotype .Two patients with 21 -OHD and their families were investigated . CYP 21 A 2 gene mutation was analyzed by PCR and direct sequencing .The probands from family 1 and 2 have been respectively diagnosed with simple virilizing and non-classical 21 -OHD . Both showed increased baseline serum 17 hydroxyprogesterone , testosterone and adrenocorticotropic hormone (ACTH ), but had no evidence of salt loss . Computer tomography revealed bilateral adrenal hyperplasia in both patients . After 1 year treatment , both had conceived successfully . DNA sequencing revealed that the proband of family 1 had compound heterozygous mutations for IVS 2 13 A >G and Ile 172 A sn . Her father was heterozygous for Ile 172 A sn , whilst her mother and brother were heterozygous for IVS 213 A /C >G . In family 2 , the proband was heterozygous for Arg 341 T rp and Gln 318 X . Her father , sister and nephew were heterozygous for Arg 341 T rp , whilst her mother was heterozygous for Gln 318 X . her brother and niece were non-affected . Carriers of single heterozygous mutations in both families had no clinical sign .In both families , the disease has been caused by compound heterozygous mutations , for which there has been a good genotype-phenotype agreement . Screening of CYP 21 A 2 gene can facilitate both diagnosis and genetic counseling .