Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure.
BACKGROUND
Premature ovarian failure (POF) is defined as amenorrhoea for >6 months, occurring before the age of 40, with an FSH serum level in the menopausal range. Although Xq deletions have been known for a long time to be associated with POF, the mechanisms involved in X deletions in order to explain ovarian failure remain unknown. In order to look for potentially cryptic chromosomal imbalance, we used high-resolution genomic analysis to characterize X chromosome deletions associated with POF.


METHODS
Three patients with POF presenting terminal Xq deletions detected by conventional cytogenetics were included in the study. Genome wide microarray comparative genomic hybridization (CGH) at a resolution of 1 Mb and fluorescence in situ hybridization (FISH) was performed.


RESULTS
Microarray CGH and FISH studies characterized the three deletions as del(X)(q21.2), del(X)(q21.31) and del(X)(q22.33). Microarray CGH showed that the del(X)(q21.31) was also associated with a Xpter duplication including the SHOX gene. In these patients with POF, deletions or duplications of autosomes have been excluded.


CONCLUSIONS
This study is the first one using microarray in patients with POF. It demonstrates that putative X chromosome deletions can be associated with other chromosomal imbalances such as duplications, and therefore illustrates the use of microarray CGH to screen chromosomal abnormalities in patients with POF.
Tachdjian
Gérard
G
Service de Biologie et Génétique de la Reproduction, Inserm U782, Université Paris 11, Hôpital A Béclère, Clamart, France.
Aboura
Azzedine
A
Portnoï
Marie-France
MF
Pasquier
Maud
M
Bourcigaux
Nathalie
N
Simon
Tabassome
T
Rousseau
Ghislaine
G
Finkel
Lina
L
Benkhalifa
Moncef
M
Christin-Maitre
Sophie
S
D000328:Adult; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D000074122:Short Stature Homeobox Protein
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein