Hum. Reprod. Advance Access originally published online on November 1, 2007
Human Reproduction 2008 23(1):222-226; doi:10.1093/humrep/dem358
Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure
1 Service de Biologie et Génétique de la Reproduction, Inserm U782, Université Paris 11, Hôpital A Béclère, Clamart, France 2 Laboratoire de Cytogénétique, Hôpital R. Debré, Paris, France 3 Laboratoire de Cytogénétique, Université Pierre et Marie Curie, Assistance-Publique Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France 4 UPRES 1533, Université Pierre et Marie Curie, Service d’Endocrinologie de la Reproduction, Assistance-Publique Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France 5 URC-EST Hôpital, Saint-Antoine, France 6 ATL R and D, Reproductive Biology and Genetics Laboratory, La Verriere, France
7 Correspondence address. Reproductive Endocrine Unit, Hôpital Saint-Antoine, EA 1533, 184 rue du faubourg Saint-Antoine, 75012 Paris, France. Tel: +33-1-49282400; Fax: +33-1-49283195; E-mail: sophie.christin-maitre{at}sat.aphp.fr
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.
CONCLUSION: 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.
Key words: deletion/duplication/microarray CGH/premature ovarian failure/X chromosome
Submitted on July 26, 2007; resubmitted on October 5, 2007; accepted on October 9, 2007.