Bilateral Perisylvian Polymicrogyria, Intellectual Disability and Nephronophthisis Associated With Compound Heterozygous Pathogenic Variants in the CEP83 Gene
Year: 2024
Type: article
Study design: Case Report
Abstract: 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.
DOI: 10.1002/ajmg.a.63863
Institutions: Meyer Children's Hospital, University of Florence
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,490
Awards: G2206487669, G3105255457
OpenAlex ID: W4402118289