A. Dardis et al., MUTATIONS OF THE STEROID 21-HYDROXYLASE GENE IN AN ARGENTINEAN POPULATION OF 36 PATIENTS WITH CLASSICAL CONGENITAL ADRENAL-HYPERPLASIA, Journal of pediatric endocrinology & metabolism, 10(1), 1997, pp. 55-61
In several studies carried out in USA and Europe, gene deletions, larg
e gene conversions and six point mutations accounted for over 90% of t
he mutated alleles reported in classical congenital hyperplasia (CAH).
In order to know the relative frequencies of mutations in a Latin-Ame
rican population, the CYP21 active gene was analyzed in 42 patients wi
th CAH belonging to 36 families attending two Argentinian clinics. The
salt wasting form was diagnosed in 24 index cases and the simple viri
lized form in 12. When available, parents were also studied. DNA was e
xtracted from peripheral blood leukocytes and specific PCR amplificati
on of four different fragments of the CYP21 gene was carried out, foll
owed by electrophoresis of the amplified product. The four fragments i
nclude segments of the gene containing the sis most frequently reporte
d abnormalities in classical CAH: IN2, EX3,R356W, cluster EX6 and I172
N. Point mutations were studied by allelic specific oligonucleotide hy
bridization; Q318X was studied by digestion of the PCR product with Ps
T1 restriction enzyme and electrophoresis on 6% nondenaturing polyacry
lamide gels. Deletions and macroconversions as well as confirmation of
homozygote point mutations were studied by Southern blotting. Percent
age distribution of abnormalities was as follows: deletion/macroconver
sion 18, IN2 18, I172N 15.3, Q318X 13.8, R356W 5.5, EX3 2.7, cluster E
X6 0, not characterized 26.7. The complete genotype could be determine
d in 20 families while in 12 additional ones, the mutation was detecte
d in one allele. Deletion/macroconversion, IN2, EX3 and Q318X were det
ected more frequently in salt wasting patients while I172N and R356W w
ere found in simple virilized patients. However, genotype was not alwa
ys concordant with phenotype. It is concluded that there are differenc
es in the frequency of several gene mutations and in that of deletion/
macroconversion between this Latin-American population and several rep
orted American and European populations. In particular the percentage
of deletion/macroconversion, IN2, EX3 and cluster EX6 was lower while
I172N was higher in our Latin-American population. Furthermore the fre
quency of mutations not characterized was larger. This: information is
useful to delineate appropriate strategies for prenatal diagnosis in
this particular population.