Back to Search Start Over

Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci

Authors :
Karine Morcel
Tanguy Watrin
Véronique David
Cédric Le Caignec
Lucie Rochard
Claude Bendavid
Bernard-Jean Paniel
Isabelle Pellerin
Christèle Dubourg
Daniel Guerrier
Sylvie Odent
Laurent Pasquier
Philippe Loget
Institut de Génétique et Développement de Rennes (IGDR)
Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)
Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes]
CHU Pontchaillou [Rennes]
Service de génétique clinique [Rennes]
Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud
Service de Génétique Médicale
Institut du thorax
Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)
Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes]
Service de pathologie
hôpital Sud
Service de Gynécologie-Obstétrique
CHI Créteil
This work was supported by the CNRS and by grants from 'Rennes Métropole', 'Conseil Régional de Bretagne', and 'La Fondation Langlois'. D. Guerrier is a permanent researcher at the 'Institut National de la Recherche Médicale (INSERM)'.
Université de Rennes 1 (UR1)
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Service de Génétique Clinique
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-hôpital Sud
Laboratoire de Génétique Moléculaire et Hormonologie
Hôpital Pontchaillou
De Villemeur, Hervé
Source :
Orphanet Journal of Rare Diseases, Orphanet Journal of Rare Diseases, 2011, 6 (1), pp.9. ⟨10.1186/1750-1172-6-9⟩, Orphanet Journal of Rare Diseases, Vol 6, Iss 1, p 9 (2011), Orphanet Journal of Rare Diseases, BioMed Central, 2011, 6 (1), pp.9. ⟨10.1186/1750-1172-6-9⟩
Publication Year :
2011
Publisher :
HAL CCSD, 2011.

Abstract

Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences. Methods We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS. The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis. Results We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome. Conclusion Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling.

Details

Language :
English
ISSN :
17501172
Database :
OpenAIRE
Journal :
Orphanet Journal of Rare Diseases, Orphanet Journal of Rare Diseases, 2011, 6 (1), pp.9. ⟨10.1186/1750-1172-6-9⟩, Orphanet Journal of Rare Diseases, Vol 6, Iss 1, p 9 (2011), Orphanet Journal of Rare Diseases, BioMed Central, 2011, 6 (1), pp.9. ⟨10.1186/1750-1172-6-9⟩
Accession number :
edsair.doi.dedup.....7f3e4b03d229dd671ce518f065a24c89