The genetics of Mullerian aplasia

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome consists of Mullerian aplasia with or without other anomalies, most commonly renal and skeletal. The genetic etiology of MRKH syndrome is unknown for most patients, but supportive evidence exists for heterozygous mutations in WNT4, LHX1, and HNF1B. Chromosomal microarray analyses have demonstrated chromosomal regions with copy number variants in multiple patients-deletions in17q12 and 16p11.2, and either deletions or duplications in 22q11.2. Genomic analyses of expression and methylation have also suggested potential molecular pathways. Positional cloning in MRKH patients with chromosomal rearrangements and exome sequencing are likely to result in new genes. Although some single gene defects and copy number variant regions have been identified, the molecular basis for the vast majority of MRKH remains unknown.