Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports.
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.


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.


CONCLUSIONS
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.
Bernardini
Laura
L
Casa Sollievo della Sofferenza Hospital, IRCCS, S San Giovanni Rotondo, Italy. l.bernardini@css-mendel.it
Gimelli
Stefania
S
Gervasini
Cristina
C
Carella
Massimo
M
Baban
Anwar
A
Frontino
Giada
G
Barbano
Giancarlo
G
Divizia
Maria Teresa
MT
Fedele
Luigi
L
Novelli
Antonio
A
Béna
Frédérique
F
Lalatta
Faustina
F
Miozzo
Monica
M
Dallapiccola
Bruno
B
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000002:abnormalities; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D055028:Comparative Genomic Hybridization; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D060850:LIM-Homeodomain Proteins; D013577:Syndrome; D014157:Transcription Factors; D014599:Uterus / Q000002:abnormalities; D014621:Vagina / Q000002:abnormalities
C496495:HNF1B protein, human; D018398:Homeodomain Proteins; C085473:LHX1 protein, human; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta