Simon Guignard Ph.D. , Christina Guillaume M.D. , Laurie Tornero M.D. , Jessika Moreau M.D. , Manon Carles Pharm.D. , François Isus M.D. , Éric Huyghe M.D., Ph.D. , Célia Ravel M.D., Ph.D. , Nathalie Vergnolle Ph.D. , Céline Deraison Ph.D. , Chrystelle Bonnart Ph.D. , Nicolas Gatimel Pharm.D., Ph.D.
{"title":"一个病例报告：CATSPER2 基因突变与听力损失导致的不明原因不孕症和受精失败的家族背景有关。","authors":"Simon Guignard Ph.D. , Christina Guillaume M.D. , Laurie Tornero M.D. , Jessika Moreau M.D. , Manon Carles Pharm.D. , François Isus M.D. , Éric Huyghe M.D., Ph.D. , Célia Ravel M.D., Ph.D. , Nathalie Vergnolle Ph.D. , Céline Deraison Ph.D. , Chrystelle Bonnart Ph.D. , Nicolas Gatimel Pharm.D., Ph.D.","doi":"10.1016/j.xfre.2023.12.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To explore the functional implications of a homozygous <em>CATSPER 2</em> (cation channel for sperm) deletion within the acrosome reaction pathway during fertilization in 2 brothers, who have unexplained infertility and hearing loss.</p></div><div><h3>Design</h3><p>Case report.</p></div><div><h3>Patients</h3><p>Two twin brothers aged 30 years with hearing loss and unexplained infertility.</p></div><div><h3>Exposure or Intervention</h3><p>Molecular genetic diagnosis of deafness. Evaluation of the acrosome reaction and calcium mobilization assays after induction by progesterone and ionomycin on spermatozoa of the <em>CATSPER 2</em>-mutated patient and on fertile controls.</p></div><div><h3>Main Outcome Measures</h3><p>Fertilization rate during conventional in vitro fertilization. Molecular genetic test. Percentage of acrosome-reacted spermatozoa with peanut agglutinin lectin staining. Recording of progesterone and ionomycin-induced intracellular calcium signals with a fluorescent probe.</p></div><div><h3>Results</h3><p>Mr. S and his brother have normal, conventional sperm parameters. Both brothers have had repeated intrauterine insemination failures and one fertilization failure after conventional in vitro fertilization. Mr. S obtained 2 healthy babies after intracytoplasmic sperm injection. Genetic analysis found a homozygote deletion of the <em>STRC</em> (stereocilin) gene (NM 153700: c.1-? 5328+?del) that removes the <em>CATSPER 2</em> gene. Mutation of the <em>STRC</em> gene is known to be associated with hearing loss. Sperm functional tests revealed an inability of progesterone to activate intracellular calcium signaling and to induce acrosome reaction.</p></div><div><h3>Conclusion</h3><p>We demonstrate the absence of a calcium signal and acrosome reaction after progesterone in our patient with a <em>CATSPER 2</em> mutation. We emphasize the importance of the male medical interview and of the genetic investigation of hearing loss. We show that in vitro fertilization–intracytoplasmic sperm injection is necessary, even where normal sperm parameters are present.</p></div>","PeriodicalId":34409,"journal":{"name":"FS Reports","volume":"5 1","pages":"Pages 114-122"},"PeriodicalIF":0.0000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666334123001356/pdfft?md5=d8d2ddd4a5d997c4d04a343ad347e0fc&pid=1-s2.0-S2666334123001356-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Involvement of CATSPER 2 mutation in a familial context of unexplained infertility and fertilization failure associated with hearing loss: a case report\",\"authors\":\"Simon Guignard Ph.D. , Christina Guillaume M.D. , Laurie Tornero M.D. , Jessika Moreau M.D. , Manon Carles Pharm.D. , François Isus M.D. , Éric Huyghe M.D., Ph.D. , Célia Ravel M.D., Ph.D. , Nathalie Vergnolle Ph.D. , Céline Deraison Ph.D. , Chrystelle Bonnart Ph.D. , Nicolas Gatimel Pharm.D., Ph.D.\",\"doi\":\"10.1016/j.xfre.2023.12.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>To explore the functional implications of a homozygous <em>CATSPER 2</em> (cation channel for sperm) deletion within the acrosome reaction pathway during fertilization in 2 brothers, who have unexplained infertility and hearing loss.</p></div><div><h3>Design</h3><p>Case report.</p></div><div><h3>Patients</h3><p>Two twin brothers aged 30 years with hearing loss and unexplained infertility.</p></div><div><h3>Exposure or Intervention</h3><p>Molecular genetic diagnosis of deafness. Evaluation of the acrosome reaction and calcium mobilization assays after induction by progesterone and ionomycin on spermatozoa of the <em>CATSPER 2</em>-mutated patient and on fertile controls.</p></div><div><h3>Main Outcome Measures</h3><p>Fertilization rate during conventional in vitro fertilization. Molecular genetic test. Percentage of acrosome-reacted spermatozoa with peanut agglutinin lectin staining. Recording of progesterone and ionomycin-induced intracellular calcium signals with a fluorescent probe.</p></div><div><h3>Results</h3><p>Mr. S and his brother have normal, conventional sperm parameters. Both brothers have had repeated intrauterine insemination failures and one fertilization failure after conventional in vitro fertilization. Mr. S obtained 2 healthy babies after intracytoplasmic sperm injection. Genetic analysis found a homozygote deletion of the <em>STRC</em> (stereocilin) gene (NM 153700: c.1-? 5328+?del) that removes the <em>CATSPER 2</em> gene. Mutation of the <em>STRC</em> gene is known to be associated with hearing loss. Sperm functional tests revealed an inability of progesterone to activate intracellular calcium signaling and to induce acrosome reaction.</p></div><div><h3>Conclusion</h3><p>We demonstrate the absence of a calcium signal and acrosome reaction after progesterone in our patient with a <em>CATSPER 2</em> mutation. We emphasize the importance of the male medical interview and of the genetic investigation of hearing loss. We show that in vitro fertilization–intracytoplasmic sperm injection is necessary, even where normal sperm parameters are present.</p></div>\",\"PeriodicalId\":34409,\"journal\":{\"name\":\"FS Reports\",\"volume\":\"5 1\",\"pages\":\"Pages 114-122\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2666334123001356/pdfft?md5=d8d2ddd4a5d997c4d04a343ad347e0fc&pid=1-s2.0-S2666334123001356-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"FS Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666334123001356\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"FS Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666334123001356","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Involvement of CATSPER 2 mutation in a familial context of unexplained infertility and fertilization failure associated with hearing loss: a case report
Objective
To explore the functional implications of a homozygous CATSPER 2 (cation channel for sperm) deletion within the acrosome reaction pathway during fertilization in 2 brothers, who have unexplained infertility and hearing loss.
Design
Case report.
Patients
Two twin brothers aged 30 years with hearing loss and unexplained infertility.
Exposure or Intervention
Molecular genetic diagnosis of deafness. Evaluation of the acrosome reaction and calcium mobilization assays after induction by progesterone and ionomycin on spermatozoa of the CATSPER 2-mutated patient and on fertile controls.
Main Outcome Measures
Fertilization rate during conventional in vitro fertilization. Molecular genetic test. Percentage of acrosome-reacted spermatozoa with peanut agglutinin lectin staining. Recording of progesterone and ionomycin-induced intracellular calcium signals with a fluorescent probe.
Results
Mr. S and his brother have normal, conventional sperm parameters. Both brothers have had repeated intrauterine insemination failures and one fertilization failure after conventional in vitro fertilization. Mr. S obtained 2 healthy babies after intracytoplasmic sperm injection. Genetic analysis found a homozygote deletion of the STRC (stereocilin) gene (NM 153700: c.1-? 5328+?del) that removes the CATSPER 2 gene. Mutation of the STRC gene is known to be associated with hearing loss. Sperm functional tests revealed an inability of progesterone to activate intracellular calcium signaling and to induce acrosome reaction.
Conclusion
We demonstrate the absence of a calcium signal and acrosome reaction after progesterone in our patient with a CATSPER 2 mutation. We emphasize the importance of the male medical interview and of the genetic investigation of hearing loss. We show that in vitro fertilization–intracytoplasmic sperm injection is necessary, even where normal sperm parameters are present.
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