Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia
Abstract Background Little is known about the genetic contribution to Müllerian aplasia, better known to patients as Mayer-Rokitansky-Küster-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...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13039-018-0359-3 |
| _version_ | 1818528861419208704 |
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| author | Durkadin Demir Eksi Yiping Shen Munire Erman Lynn P. Chorich Megan E. Sullivan Meric Bilekdemir Elanur Yılmaz Guven Luleci Hyung-Goo Kim Ozgul M. Alper Lawrence C. Layman |
| author_facet | Durkadin Demir Eksi Yiping Shen Munire Erman Lynn P. Chorich Megan E. Sullivan Meric Bilekdemir Elanur Yılmaz Guven Luleci Hyung-Goo Kim Ozgul M. Alper Lawrence C. Layman |
| author_sort | Durkadin Demir Eksi |
| collection | DOAJ |
| description | Abstract Background Little is known about the genetic contribution to Müllerian aplasia, better known to patients as Mayer-Rokitansky-Küster-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. |
| first_indexed | 2024-12-11T06:55:32Z |
| format | Article |
| id | doaj.art-bcbb663442044972bea523c7d3c2c957 |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-12-11T06:55:32Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
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| series | Molecular Cytogenetics |
| spelling | doaj.art-bcbb663442044972bea523c7d3c2c9572022-12-22T01:16:46ZengBMCMolecular Cytogenetics1755-81662018-02-011111810.1186/s13039-018-0359-3Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasiaDurkadin Demir Eksi0Yiping Shen1Munire Erman2Lynn P. Chorich3Megan E. Sullivan4Meric Bilekdemir5Elanur Yılmaz6Guven Luleci7Hyung-Goo Kim8Ozgul M. Alper9Lawrence C. Layman10Department of Medical Biology, Alanya Alaaddin Keykubat University, Faculty of MedicineGuangxi Maternal and Child Health HospitalDepartment of Obstetrics and Gynecology, Akdeniz University, Faculty of MedicineSection of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology Medical College of Georgia at Augusta UniversitySection of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology Medical College of Georgia at Augusta UniversityDepartment of Obstetrics and Gynecology, Akdeniz University, Faculty of MedicineDepartment of Medical Biology and Genetics, Akdeniz University, Faculty of MedicineDepartment of Medical Biology and Genetics, Akdeniz University, Faculty of MedicineSection of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology Medical College of Georgia at Augusta UniversityDepartment of Medical Biology and Genetics, Akdeniz University, Faculty of MedicineSection of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology Medical College of Georgia at Augusta UniversityAbstract Background Little is known about the genetic contribution to Müllerian aplasia, better known to patients as Mayer-Rokitansky-Küster-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.http://link.springer.com/article/10.1186/s13039-018-0359-3Müllerian aplasiaMayer-Rokitansky-Küster-Hauser syndromeMRKHCongenital absence of the uterus and vaginaCopy number variantCNV |
| spellingShingle | Durkadin Demir Eksi Yiping Shen Munire Erman Lynn P. Chorich Megan E. Sullivan Meric Bilekdemir Elanur Yılmaz Guven Luleci Hyung-Goo Kim Ozgul M. Alper Lawrence C. Layman Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia Molecular Cytogenetics Müllerian aplasia Mayer-Rokitansky-Küster-Hauser syndrome MRKH Congenital absence of the uterus and vagina Copy number variant CNV |
| title | Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia |
| title_full | Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia |
| title_fullStr | Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia |
| title_full_unstemmed | Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia |
| title_short | Copy number variation and regions of homozygosity analysis in patients with MÜLLERIAN aplasia |
| title_sort | copy number variation and regions of homozygosity analysis in patients with mullerian aplasia |
| topic | Müllerian aplasia Mayer-Rokitansky-Küster-Hauser syndrome MRKH Congenital absence of the uterus and vagina Copy number variant CNV |
| url | http://link.springer.com/article/10.1186/s13039-018-0359-3 |
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