Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?

Vilma Mantovani; Elisabetta Dondi; Daniela Larizza; Mariangela Cisternino; Michela Bragliani; Mariagabriella Viggiani; Miryam Martinetti; Mariaclara Cuccia

doi:10.1038/sj/ejhg/5200778

Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?

Vilma Mantovani, Elisabetta Dondi, Daniela Larizza, Mariangela Cisternino, Michela Bragliani, Mariagabriella Viggiani, Miryam Martinetti, Mariaclara Cuccia

IRCCS Fondazione Policlinico San Matteo

Research output: Contribution to journal › Article

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.

Original language	English
Pages (from-to)	137-140
Number of pages	4
Journal	European Journal of Human Genetics
Volume	10
Issue number	2
DOIs	https://doi.org/10.1038/sj/ejhg/5200778
Publication status	Published - 2002

Fingerprint

Sex Chromosome Aberrations

Steroid 21-Hydroxylase

Fetus

Odds Ratio

17-alpha-Hydroxyprogesterone

Klinefelter Syndrome

Turner Syndrome

Survival

Mutation Rate

Missense Mutation

Heterozygote

Chromosome Aberrations

Genes

Exons

Pregnancy

Population

Keywords

CYP21 gene
Klinefelter syndrome
Sex chromosomes
Steroid 21-hydroxylase
Steroid 21-hydroxylase deficiency
Turner syndrome

ASJC Scopus subject areas

Genetics(clinical)

Cite this

Mantovani, V., Dondi, E., Larizza, D., Cisternino, M., Bragliani, M., Viggiani, M., ... Cuccia, M. (2002). Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations? European Journal of Human Genetics, 10(2), 137-140. https://doi.org/10.1038/sj/ejhg/5200778

Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations? / Mantovani, Vilma; Dondi, Elisabetta; Larizza, Daniela; Cisternino, Mariangela; Bragliani, Michela; Viggiani, Mariagabriella; Martinetti, Miryam; Cuccia, Mariaclara.

In: European Journal of Human Genetics, Vol. 10, No. 2, 2002, p. 137-140.

Research output: Contribution to journal › Article

Mantovani, V, Dondi, E, Larizza, D, Cisternino, M, Bragliani, M, Viggiani, M, Martinetti, M & Cuccia, M 2002, 'Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?', European Journal of Human Genetics, vol. 10, no. 2, pp. 137-140. https://doi.org/10.1038/sj/ejhg/5200778

Mantovani V, Dondi E, Larizza D, Cisternino M, Bragliani M, Viggiani M et al. Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations? European Journal of Human Genetics. 2002;10(2):137-140. https://doi.org/10.1038/sj/ejhg/5200778

Mantovani, Vilma ; Dondi, Elisabetta ; Larizza, Daniela ; Cisternino, Mariangela ; Bragliani, Michela ; Viggiani, Mariagabriella ; Martinetti, Miryam ; Cuccia, Mariaclara. / Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?. In: European Journal of Human Genetics. 2002 ; Vol. 10, No. 2. pp. 137-140.

@article{8b74644a99ef4005b5af22f78a34cee6,

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.",

keywords = "CYP21 gene, Klinefelter syndrome, Sex chromosomes, Steroid 21-hydroxylase, Steroid 21-hydroxylase deficiency, Turner syndrome",

author = "Vilma Mantovani and Elisabetta Dondi and Daniela Larizza and Mariangela Cisternino and Michela Bragliani and Mariagabriella Viggiani and Miryam Martinetti and Mariaclara Cuccia",

year = "2002",

doi = "10.1038/sj/ejhg/5200778",

language = "English",

volume = "10",

pages = "137--140",

journal = "European Journal of Human Genetics",

issn = "1018-4813",