Ruth McGowan1, Graham Tydeman2, David Shapiro3, Tracey Craig4, Norma Morrison4, Susan Logan5, Adam H Balen6, S Faisal Ahmed7, Miriam Deeny8, John Tolmie9, Edward S Tobias10. 1. West of Scotland Clinical Genetics Service, Southern General Hospital, Glasgow, United Kingdom. Electronic address: ruthmcgowan@nhs.net. 2. Department of Obstetrics and Gynaecology, Victoria Hospital, Kirkcaldy, United Kingdom. 3. Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom. 4. Laboratory Genetics, Southern General Hospital, Glasgow, United Kingdom. 5. Department of Obstetrics and Gynaecology, National University Hospital, Singapore. 6. Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, United Kingdom. 7. Section of Child Health, University of Glasgow, Royal Hospital for Sick Children, Yorkhill, United Kingdom. 8. Department of Gynaecology, Glasgow Royal Infirmary, Glasgow, United Kingdom. 9. West of Scotland Clinical Genetics Service, Southern General Hospital, Glasgow, United Kingdom. 10. School of Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Abstract
OBJECTIVE: To clinically and genetically investigate women with müllerian disorders, including Mayer-Rokitanksy-Kuster-Hauser (MRKH) syndrome. DESIGN: Two-year prospective clinical and laboratory study. SETTING: Not applicable. PATIENT(S): Thirty-five women over 16 years of age with a müllerian disorder, including MRKH. INTERVENTION(S): 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. RESULT(S): 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. CONCLUSION(S): 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.
OBJECTIVE: To clinically and genetically investigate women with müllerian disorders, including Mayer-Rokitanksy-Kuster-Hauser (MRKH) syndrome. DESIGN: Two-year prospective clinical and laboratory study. SETTING: Not applicable. PATIENT(S): Thirty-five women over 16 years of age with a müllerian disorder, including MRKH. INTERVENTION(S): 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. RESULT(S): 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. CONCLUSION(S): 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.
Authors: Laura Santana Gonzalez; Ioanna A Rota; Mara Artibani; Matteo Morotti; Zhiyuan Hu; Nina Wietek; Abdulkhaliq Alsaadi; Ashwag Albukhari; Tatjana Sauka-Spengler; Ahmed A Ahmed Journal: Front Cell Dev Biol Date: 2021-03-08
Authors: Sasha Mikhael; Sonal Dugar; Madison Morton; Lynn P Chorich; Kerlene Berwick Tam; Amy C Lossie; Hyung-Goo Kim; James Knight; Hugh S Taylor; Souhrid Mukherjee; John A Capra; John A Phillips; Michael Friez; Lawrence C Layman Journal: Hum Genet Date: 2021-01-19 Impact factor: 5.881
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