TY - JOUR
T1 - Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?
AU - Mantovani, Vilma
AU - Dondi, Elisabetta
AU - Larizza, Daniela
AU - Cisternino, Mariangela
AU - Bragliani, Michela
AU - Viggiani, Mariagabriella
AU - Martinetti, Miryam
AU - Cuccia, Mariaclara
PY - 2002
Y1 - 2002
N2 - We investigated whether molecular defects in the CYP21 gene were detectable in two common sex chromosome aberrations, the Turner and the Klinefelter syndromes. We found abnormal 17-hydroxyprogesterone levels after adrenal stimulation in 26/60 (43.3%) patients affected by these chromosome aberrations, as compared with only 11/68 (16.2%) normal controls (P=0.0014, odds ratio 4.0). Screening of the CYP21 gene identified a single Val281Leu missense mutation in exon 7 in 9/63 (14.3%) of the patients, all nine of whom were heterozygote carriers; the mutation frequency was significantly higher than in the general population (P=0.007, odds ratio=3.5). The hormonal and molecular data indicate that these common sex chromosome aberrations are associated with a remarkably high frequency of steroidogenic defects. It may be hypothesised that reduced levels of steroid 21-hydroxylase could confer a survival advantage, leading to a successful pregnancy.
AB - We investigated whether molecular defects in the CYP21 gene were detectable in two common sex chromosome aberrations, the Turner and the Klinefelter syndromes. We found abnormal 17-hydroxyprogesterone levels after adrenal stimulation in 26/60 (43.3%) patients affected by these chromosome aberrations, as compared with only 11/68 (16.2%) normal controls (P=0.0014, odds ratio 4.0). Screening of the CYP21 gene identified a single Val281Leu missense mutation in exon 7 in 9/63 (14.3%) of the patients, all nine of whom were heterozygote carriers; the mutation frequency was significantly higher than in the general population (P=0.007, odds ratio=3.5). The hormonal and molecular data indicate that these common sex chromosome aberrations are associated with a remarkably high frequency of steroidogenic defects. It may be hypothesised that reduced levels of steroid 21-hydroxylase could confer a survival advantage, leading to a successful pregnancy.
KW - CYP21 gene
KW - Klinefelter syndrome
KW - Sex chromosomes
KW - Steroid 21-hydroxylase
KW - Steroid 21-hydroxylase deficiency
KW - Turner syndrome
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U2 - 10.1038/sj/ejhg/5200778
DO - 10.1038/sj/ejhg/5200778
M3 - Article
C2 - 11938445
VL - 10
SP - 137
EP - 140
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -