Copy number variation and regions of homozygosity analysis in patients with MULLERIAN aplasia

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dc.contributor.authorEkşi, Durkadın Demir
dc.contributor.authorShen, Yiping
dc.contributor.authorErman, Münire
dc.contributor.authorChorich, Lynn P.
dc.contributor.authorSullivan, Megan E.
dc.contributor.authorBilekdemir, Meriç
dc.contributor.authorLayman, Lawrence C.
dc.date.accessioned2021-02-19T21:16:38Z
dc.date.available2021-02-19T21:16:38Z
dc.date.issued2018
dc.departmentALKÜ
dc.descriptionYilmaz, Elanur/0000-0001-7045-5068; Alper, Ozgul/0000-0003-1536-2111
dc.description.abstractBackground: Little is known about the genetic contribution to Mullerian aplasia, better known to patients as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Mutations in two genes (WNT4 and HNF1B) account for a small number of patients, but heterozygous copy number variants (CNVs) have been described. However, the significance of these CNVs in the pathogenesis of MRKH is unknown, but suggests possible autosomal dominant inheritance. We are not aware of CNV studies in consanguineous patients, which could pinpoint genes important in autosomal recessive MRKH. We therefore utilized SNP/CGH microarrays to identify CNVs and define regions of homozygosity (ROH) in Anatolian Turkish MRKH patients. Result(s): Five different CNVs were detected in 4/19 patients (21%), one of which is a previously reported 16p11.2 deletion containing 32 genes, while four involved smaller regions each containing only one gene. Fourteen of 19 (74%) of patients had parents that were third degree relatives or closer. There were 42 regions of homozygosity shared by at least two MRKH patients which was spread throughout most chromosomes. Of interest, eight candidate genes suggested by human or animal studies (RBM8A, CMTM7, CCR4, TRIM71, CNOT10, TP63, EMX2, and CFTR) reside within these ROH. Conclusion(s): CNVs were found in about 20% of Turkish MRKH patients, and as in other studies, proof of causation is lacking. The 16p11.2 deletion seen in mixed populations is also identified in Turkish MRKH patients. Turkish MRKH patients have a higher likelihood of being consanguineous than the general Anatolian Turkish population. Although identified single gene mutations and heterozygous CNVs suggest autosomal dominant inheritance for MRKH in much of the western world, regions of homozygosity, which could contain shared mutant alleles, make it more likely that autosomal recessively inherited causes will be manifested in Turkish women with MRKH.
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HD33004]; Department of Ob/Gyn at Augusta University; Research Funds Office of Akdeniz University, Antalya, Turkey [2012. 03.0122.001]
dc.description.sponsorshipLCL was funded by NIH HD33004 and the Department of Ob/Gyn at Augusta University and OMA was funded by the Research Funds Office of Akdeniz University, Antalya, Turkey (Grant #2012. 03.0122.001).
dc.identifier.doi10.1186/s13039-018-0359-3
dc.identifier.issn1755-8166
dc.identifier.pmid29434669
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1186/s13039-018-0359-3
dc.identifier.urihttps://hdl.handle.net/20.500.12868/500
dc.identifier.volume11en_US
dc.identifier.wosWOS:000424131300001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthor0-belirlenecek
dc.language.isoen
dc.publisherBiomed Central Ltd
dc.relation.ispartofMolecular Cytogenetics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectMullerian aplasia
dc.subjectMayer-Rokitansky-Kuster-Hauser syndrome
dc.subjectMRKH
dc.subjectCongenital absence of the uterus and vagina
dc.subjectCopy number variant
dc.subjectCNV
dc.subjectCandidate gene
dc.subjectRegions of homozygosity
dc.subjectROH
dc.titleCopy number variation and regions of homozygosity analysis in patients with MULLERIAN aplasia
dc.typeArticle

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