Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect
In vitro fertilization (IVF) involves controlled ovarian hyperstimulation using hormones to produce large numbers of oocytes. The success of IVF is tightly linked to the availability of mature oocytes. In most cases, about 70% to 80% of the oocytes are mature at the time of retrieval, however, in ra...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/4/382 |
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| author | Özlem Okutman Cem Demirel Firat Tülek Veronique Pfister Umut Büyük Jean Muller Nicolas Charlet-Berguerand Stéphane Viville |
| author_facet | Özlem Okutman Cem Demirel Firat Tülek Veronique Pfister Umut Büyük Jean Muller Nicolas Charlet-Berguerand Stéphane Viville |
| author_sort | Özlem Okutman |
| collection | DOAJ |
| description | In vitro fertilization (IVF) involves controlled ovarian hyperstimulation using hormones to produce large numbers of oocytes. The success of IVF is tightly linked to the availability of mature oocytes. In most cases, about 70% to 80% of the oocytes are mature at the time of retrieval, however, in rare instances, all of them may be immature, implying that they were not able to reach the metaphase II (MII) stage. The failure to obtain any mature oocytes, despite a well conducted ovarian stimulation in repeated cycles is a very rare cause of primary female infertility, for which the underlying suspected genetic factors are still largely unknown. In this study, we present the whole exome sequencing analysis of a consanguineous Turkish family comprising three sisters with a recurrent oocyte maturation defect. Analysis of the data reveals a homozygous splice site mutation (c.1775-3C>A) in the zona pellucida glycoprotein 1 (<i>ZP1</i>) gene. Minigene experiments show that the mutation causes the retention of the intron 11 sequence between exon 11 and exon 12, resulting in a frameshift and the likely production of a truncated protein. |
| first_indexed | 2024-03-10T20:45:04Z |
| format | Article |
| id | doaj.art-98c44adfb71c41b99b515a94148e3648 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T20:45:04Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-98c44adfb71c41b99b515a94148e36482023-11-19T20:24:17ZengMDPI AGGenes2073-44252020-04-0111438210.3390/genes11040382Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation DefectÖzlem Okutman0Cem Demirel1Firat Tülek2Veronique Pfister3Umut Büyük4Jean Muller5Nicolas Charlet-Berguerand6Stéphane Viville7Institut de Parasitologie et Pathologie Tropicale, EA 7292, Fédération de Médecine Translationelle (IPPTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, FranceMemorial Atasehir Hospital, In Vitro Fertilization (IVF) Andrology and Genetics Center, Kucukbakkalkoy mh.Vedat Gunyol cd No:28-30, 34758 Atasehir/Istanbul, TurkeyMemorial Atasehir Hospital, In Vitro Fertilization (IVF) Andrology and Genetics Center, Kucukbakkalkoy mh.Vedat Gunyol cd No:28-30, 34758 Atasehir/Istanbul, TurkeyMédecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM), U964/Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg, 67404 Illkirch, FranceHibrigen Biotechnology R&D Industry and Trade Ltd. Co.,Tubitak MAM Teknoloji Serbest Bolgesi, Baris SB Mh 5002.sk Yeni Tek. Binasi ABlok 4, A/101 Gebze/Kocaeli, TurkeyLaboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, FranceMédecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM), U964/Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg, 67404 Illkirch, FranceInstitut de Parasitologie et Pathologie Tropicale, EA 7292, Fédération de Médecine Translationelle (IPPTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, FranceIn vitro fertilization (IVF) involves controlled ovarian hyperstimulation using hormones to produce large numbers of oocytes. The success of IVF is tightly linked to the availability of mature oocytes. In most cases, about 70% to 80% of the oocytes are mature at the time of retrieval, however, in rare instances, all of them may be immature, implying that they were not able to reach the metaphase II (MII) stage. The failure to obtain any mature oocytes, despite a well conducted ovarian stimulation in repeated cycles is a very rare cause of primary female infertility, for which the underlying suspected genetic factors are still largely unknown. In this study, we present the whole exome sequencing analysis of a consanguineous Turkish family comprising three sisters with a recurrent oocyte maturation defect. Analysis of the data reveals a homozygous splice site mutation (c.1775-3C>A) in the zona pellucida glycoprotein 1 (<i>ZP1</i>) gene. Minigene experiments show that the mutation causes the retention of the intron 11 sequence between exon 11 and exon 12, resulting in a frameshift and the likely production of a truncated protein.https://www.mdpi.com/2073-4425/11/4/382immature oocytesoocyte maturation defectfemale infertility |
| spellingShingle | Özlem Okutman Cem Demirel Firat Tülek Veronique Pfister Umut Büyük Jean Muller Nicolas Charlet-Berguerand Stéphane Viville Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect Genes immature oocytes oocyte maturation defect female infertility |
| title | Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect |
| title_full | Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect |
| title_fullStr | Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect |
| title_full_unstemmed | Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect |
| title_short | Homozygous Splice Site Mutation in <i>ZP1</i> Causes Familial Oocyte Maturation Defect |
| title_sort | homozygous splice site mutation in i zp1 i causes familial oocyte maturation defect |
| topic | immature oocytes oocyte maturation defect female infertility |
| url | https://www.mdpi.com/2073-4425/11/4/382 |
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