Research
Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports
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* Corresponding author: Bruno Dallapiccola dallapiccola@css-mendel.it
1 "Casa Sollievo della Sofferenza" Hospital, IRCCS, S San Giovanni Rotondo, Italy
2 Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland
3 Division of Medical Genetics, San Paolo School of Medicine, University of Milan, Milan, Italy
4 Molecular Genetics Unit, G Gaslini Children's Hospital, Genoa, Italy
5 Cardiology Unit, Molecular Genetics Unit, G Gaslini Children's Hospital, Genoa, Italy
6 Department of Obstetrics, Gynaecology and Neonatology, Fondazione Policlinico-Mangiagalli-Regina Elena, University of Milan, Italy
7 Department of Nephrology, G Gaslini Children's Hospital, Genoa, Italy
8 Clinical Genetic Unit, Department of Obstetrics and Pediatrics, University of Milan, Fondazione Policlinico-Mangiagalli-Regina Elena, University of Milan, Italy
Orphanet Journal of Rare Diseases 2009, 4:25 doi:10.1186/1750-1172-4-25
Published: 4 November 2009Abstract
Background
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.
Methods and Results
we report on two patients affected by MRKH syndrome in which array-CGH analysis disclosed an identical deletion spanning 1.5 Mb of genomic DNA at chromosome 17q12. One patient was affected by complete absence of uterus and vagina, with bilaterally normal ovaries, while the other displayed agenesis of the upper part of vagina, right unicornuate uterus, non cavitating rudimentary left horn and bilaterally multicystic kidneys. The deletion encompassed two candidate genes, TCF2 and LHX1. Mutational screening of these genes in a selected group of 20 MRKH females without 17q12 deletion was negative.
Conclusion
Deletion 17q12 is a rare albeit recurrent anomaly mediated by segmental duplications, previously reported in subjects with developmental kidney abnormalities and diabetes. The present two patients expand the clinical spectrum associated with this imbalance and suggest that this region is a candidate locus for a subset of MRKH syndrome individuals, with or without renal defects.