Elena Parrini, Simona Balestrini, Domenico Rutigliano, Maria Luisa Ricci, Davide Mei, Renzo Guerrini
{"title":"与 CEP83 基因复合杂合子致病性变异有关的双侧脐周多畸形、智力障碍和肾炎。","authors":"Elena Parrini, Simona Balestrini, Domenico Rutigliano, Maria Luisa Ricci, Davide Mei, Renzo Guerrini","doi":"10.1002/ajmg.a.63863","DOIUrl":null,"url":null,"abstract":"<p><p>The centrosomal protein 83 (CEP83) is a centriolar protein involved in primary cilium assembly, an early and critical step in ciliogenesis. Bi-allelic pathogenic variants in the CEP83 gene have been associated with infantile nephronophthisis and, in a few patients, retinitis pigmentosa. We describe a 5-year-old boy with bilateral perisylvian polymicrogyria, intellectual disability, and nephronophthisis in whom, using exome sequencing, we identified the c.1052T>G p.(Leu351*) stopgain variant inherited from the father and the c.2024T>C p.(Leu675Pro) missense variant inherited from the mother, in a compound heterozygous pattern. Polymicrogyria or, in general, malformations of cortical development had not been previously observed in patients with pathogenic CEP83 variants. However, defects in CEP83 can affect the formation and function of cilia or centrosomal structures, resulting in a polymicrogyric pattern overlapping with that associated with pathogenic variants affecting other genes coding for centrosomal components. This observation expands the spectrum of phenotypes associated with the CEP83 gene and adds it to the list of genes associated with bilateral perisylvian polymicrogyria.</p>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bilateral Perisylvian Polymicrogyria, Intellectual Disability and Nephronophthisis Associated With Compound Heterozygous Pathogenic Variants in the CEP83 Gene.\",\"authors\":\"Elena Parrini, Simona Balestrini, Domenico Rutigliano, Maria Luisa Ricci, Davide Mei, Renzo Guerrini\",\"doi\":\"10.1002/ajmg.a.63863\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The centrosomal protein 83 (CEP83) is a centriolar protein involved in primary cilium assembly, an early and critical step in ciliogenesis. Bi-allelic pathogenic variants in the CEP83 gene have been associated with infantile nephronophthisis and, in a few patients, retinitis pigmentosa. We describe a 5-year-old boy with bilateral perisylvian polymicrogyria, intellectual disability, and nephronophthisis in whom, using exome sequencing, we identified the c.1052T>G p.(Leu351*) stopgain variant inherited from the father and the c.2024T>C p.(Leu675Pro) missense variant inherited from the mother, in a compound heterozygous pattern. Polymicrogyria or, in general, malformations of cortical development had not been previously observed in patients with pathogenic CEP83 variants. However, defects in CEP83 can affect the formation and function of cilia or centrosomal structures, resulting in a polymicrogyric pattern overlapping with that associated with pathogenic variants affecting other genes coding for centrosomal components. This observation expands the spectrum of phenotypes associated with the CEP83 gene and adds it to the list of genes associated with bilateral perisylvian polymicrogyria.</p>\",\"PeriodicalId\":7507,\"journal\":{\"name\":\"American Journal of Medical Genetics Part A\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Medical Genetics Part A\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/ajmg.a.63863\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Medical Genetics Part A","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/ajmg.a.63863","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Bilateral Perisylvian Polymicrogyria, Intellectual Disability and Nephronophthisis Associated With Compound Heterozygous Pathogenic Variants in the CEP83 Gene.
The centrosomal protein 83 (CEP83) is a centriolar protein involved in primary cilium assembly, an early and critical step in ciliogenesis. Bi-allelic pathogenic variants in the CEP83 gene have been associated with infantile nephronophthisis and, in a few patients, retinitis pigmentosa. We describe a 5-year-old boy with bilateral perisylvian polymicrogyria, intellectual disability, and nephronophthisis in whom, using exome sequencing, we identified the c.1052T>G p.(Leu351*) stopgain variant inherited from the father and the c.2024T>C p.(Leu675Pro) missense variant inherited from the mother, in a compound heterozygous pattern. Polymicrogyria or, in general, malformations of cortical development had not been previously observed in patients with pathogenic CEP83 variants. However, defects in CEP83 can affect the formation and function of cilia or centrosomal structures, resulting in a polymicrogyric pattern overlapping with that associated with pathogenic variants affecting other genes coding for centrosomal components. This observation expands the spectrum of phenotypes associated with the CEP83 gene and adds it to the list of genes associated with bilateral perisylvian polymicrogyria.
期刊介绍:
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .