OBJECTIVE: To study the molecular defects of congenital adrenal hyperp
lasia (CAH). STUDY DESIGN: Twenty Chinese patients, including 8 with s
alt-wasting (SW) type CAH, II with simple virilizing (SV) type CAH and
1 with nonclassical (NC) type CAH, were recruited. Two rounds of the
polymerase chain reaction (PCR) were used to study the 21-hydroxylase
gene (CYP21). The primary PCR amplified CYP21-specific DNA fragments,
and the secondary PCR used products from the primary PCR for analysis
of amplification-created restriction sites (ACRS) and direct DNA seque
ncing. In all patients, ACRS analysis was done at 12 possible mutation
sites, and then direct DNA sequencing was performed to confirm or def
ine the molecular defects. RESULTS: Tell different mutations, includin
g nine point mutations and gross gene deletion or conversion, were fou
nd in this study. Of the nine point mutations, eight could be easily d
etected by ACRS analysis. The three most common mutations were codon (
CD)172 t-->a (I172N), IVS-II 656 c/a-->g, and gross gene deletion or c
onversion, accounting for 27.5% (11/40 alleles), 25% (10/40) and 20% (
8/40) of all identified mutations, respectively. All SW patients were
compound heterozygotes of IVS-II 656, gross gene deletion or conversio
n, or other severe defects, including CDs236 (t-->a) (I236N)+ 237 (t--
>a) (V237E)+239 (t-->a) (M239K), CD306 (+ t), CD318 (c-->t) (Q318X) an
d CD356 (c-->t) (R356W) mutations. All SV patients had one allele with
a CD172 (I172N) mutation. One allele of an NC patient had a CD183 (c-
->g) (D183E) mutation, and the other allele was not defined. In the wh
ole series,four alleles (10%) had more than one mutation. CONCLUSION:
We found 10 different mutations in this study. The correlation between
genotypes and phenotypes was compatible with the reported data. Two r
ounds of PCR and ACRS analysis may provide important information for g
enetic counseling, prenatal diagnosis and management of families at ri
sk for CAH.