DNA copy number variations are important in the complex genetic architecture of mullerian disorders

Additional congenital abnormalities and regions of genomic imbalance are common in women with mullerian disorders, including Mayer-Rokitanksy-Kuster-Hauser syndrome. These women should be thoroughly investigated, and array comparative genomic hybridization should be considered.


Ruth McGowan, M.B.Ch.B., Graham Tydeman, B.Sc., David Shapiro, Ph.D., Tracey Craig, M.Sc., Norma Morrison, Ph.D., Susan Logan, M.D., Adam H. Balen, M.D., S. Faisal Ahmed, M.D., Miriam Deeny, B.Sc., John Tolmie, B.Sc., Edward S. Tobias, Ph.D.

Volume 103, Issue 3, Pages 1021-1030



To clinically and genetically investigate women with müllerian disorders, including Mayer-Rokitanksy-Kuster-Hauser (MRKH) syndrome.


Two-year prospective clinical and laboratory study.


Not applicable.


Thirty-five women over 16 years of age with a müllerian disorder, including MRKH.


Women were recruited from specialist gynecology clinics or identified from the Scottish Disorders of Sex Development Register (www.sdsd.scot.nhs.uk/index.html). Associated abnormalities were detected by clinical examination, imaging studies, and biochemical analyses. Chromosomal microduplications and microdeletions were detected by array comparative genomic hybridization (CGH) and validated by fluorescence in situ hydridization.

Main Outcome Measure(s):

Identification of associated congenital and biochemical abnormalities and identification of regions of genomic imbalance using array CGH.


Associated congenital anomalies were common, present in 25/35 (71%) of affected women, particularly renal and skeletal abnormalities, which were present in 15/35 (43%) and 17/35 (49%) women, respectively. Using array CGH, novel or recurrent regions of genomic imbalance were identified in 4/11 (36%) women with MRKH and in 5/24 (21%) women with other müllerian abnormalities.


Additional congenital abnormalities and regions of genomic imbalance are common in women with müllerian disorders, including MRKH. Recurrent microdeletions and microduplications associated with MRKH implicate specific possibly causative genes. The investigation of women with müllerian disorders should be thorough, and array CGH should be considered, given the potential highly significant familial implications of a chromosomal abnormality.

Read the full text at: http://www.fertstert.org/article/S0015-0282(15)00045-X/fulltext