SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome.
OBJECTIVE
The Mayer-Rokitansky-Küster-Hauser syndrome is defined as congenital aplasia of müllerian ducts derived structures in females with a normal female chromosomal and gonadal sex. Most cases with Mayer-Rokitansky-Küster-Hauser syndrome are sporadic, although familial cases have been reported. The genetic basis of Mayer-Rokitansky-Küster-Hauser syndrome is largely unknown and seems heterogeneous, and a small number of cases were found to have mutations in the WNT4 gene. The aim of this study was to identify possible recurrent submicroscopic imbalances in a cohort of familial and sporadic cases with Mayer-Rokitansky-Küster-Hauser syndrome.


METHODS
Multiplex ligation-dependent probe amplification was used to screen the subtelomeric sequences of all chromosomes in 30 patients with Mayer-Rokitansky-Küster-Hauser syndrome (sporadic, n = 27 and familial, n = 3). Segregation analysis and pyrosequencing were applied to validate the MLPA results in the informative family.


RESULTS
Partial duplication of the Xpter pseudoautosomal region 1 containing the short stature homeobox (SHOX) gene was detected in five patients with Mayer-Rokitansky-Küster-Hauser syndrome (familial, n = 3 and sporadic, n = 2) and not in 53 healthy controls. The duplications were not overlapping, and SHOX was never entirely duplicated. Haplotyping in the informative family revealed that SHOX gene duplication was inherited from the unaffected father and was absent in two healthy sisters.


CONCLUSIONS
Partial duplication of SHOX gene is found in some cases with both familial and sporadic Mayer-Rokitansky-Küster-Hauser type I syndrome.
Gervasini
Cristina
C
Medical Genetics, Department of Medicine, Surgery and Dentistry, Università degli Studi di Milano, Italy.
Grati
Francesca Romana
FR
Lalatta
Faustina
F
Tabano
Silvia
S
Gentilin
Barbara
B
Colapietro
Patrizia
P
De Toffol
Simona
S
Frontino
Giada
G
Motta
Francesca
F
Maitz
Silvia
S
Bernardini
Laura
L
Dallapiccola
Bruno
B
Fedele
Luigi
L
Larizza
Lidia
L
Miozzo
Monica
M
D058489:46, XX Disorders of Sex Development / Q000235:genetics; D000015:Abnormalities, Multiple / Q000235:genetics; D000568:Amenorrhea / Q000209:etiology / Q000235:genetics; D001483:Base Sequence; D015331:Cohort Studies; D000013:Congenital Abnormalities; D005260:Female; D020440:Gene Duplication; D005820:Genetic Testing; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000002:abnormalities; D008297:Male; D025202:Molecular Diagnostic Techniques; D009095:Mullerian Ducts / Q000002:abnormalities*; D021141:Nucleic Acid Amplification Techniques; D000074122:Short Stature Homeobox Protein; D019170:Somites / Q000002:abnormalities; D013131:Spine / Q000002:abnormalities; D014599:Uterus / Q000002:abnormalities; D014621:Vagina / Q000002:abnormalities
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein