title: Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?
abstract: 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.
authors.affiliation: Laboratorio Centralizzato Settore Genetica, Policlinico S.Orsola-Malpighi, Bologna, Italy. mantovan@med.unibo.it
authors.forename: Vilma
authors.initials: V
authors.lastname: Mantovani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dondi
authors.forename: Daniela
authors.initials: D
authors.lastname: Larizza
authors.forename: Mariangela
authors.initials: M
authors.lastname: Cisternino
authors.forename: Michela
authors.initials: M
authors.lastname: Bragliani
authors.forename: Mariagabriella
authors.initials: M
authors.lastname: Viggiani
authors.forename: Miryam
authors.initials: M
authors.lastname: Martinetti
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D005260:Female; D005328:Fetal Viability / Q000235:genetics* / Q000502:physiology; D005333:Fetus / Q000502:physiology*; D006801:Humans; D007713:Klinefelter Syndrome / Q000235:genetics; D008297:Male; D009154:Mutation; D012729:Sex Chromosome Aberrations; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D014424:Turner Syndrome / Q000235:genetics
chemical_list: D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase