A novel pathogenic ATP6V1B2 variant: Widening the genotypic spectrum of the epileptic neurodevelopmental phenotype.
| Title: | A novel pathogenic ATP6V1B2 variant: Widening the genotypic spectrum of the epileptic neurodevelopmental phenotype. |
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| Authors: | Veltra D; Laboratory of Medical Genetics, School of Medicine, National & Kapodistrian University of Athens, 'St. Sophia's' Children's Hospital, Athens, Greece.; Kosma K; Laboratory of Medical Genetics, School of Medicine, National & Kapodistrian University of Athens, 'St. Sophia's' Children's Hospital, Athens, Greece.; Papavasiliou A; Department of Pediatric Neurology, Iaso Children's Hospital, Marousi, Greece.; Tilemis FN; Laboratory of Medical Genetics, School of Medicine, National & Kapodistrian University of Athens, 'St. Sophia's' Children's Hospital, Athens, Greece.; Research University Institute for the Study of Genetic and Malignant Disease of Childhood, 'St. Sophia's' Children's Hospital, Athens, Greece.; Traeger-Synodinos J; Laboratory of Medical Genetics, School of Medicine, National & Kapodistrian University of Athens, 'St. Sophia's' Children's Hospital, Athens, Greece.; Sofocleous C; Laboratory of Medical Genetics, School of Medicine, National & Kapodistrian University of Athens, 'St. Sophia's' Children's Hospital, Athens, Greece.; Research University Institute for the Study of Genetic and Malignant Disease of Childhood, 'St. Sophia's' Children's Hospital, Athens, Greece. |
| Source: | American journal of medical genetics. Part A [Am J Med Genet A] 2022 Dec; Vol. 188 (12), pp. 3563-3566. Date of Electronic Publication: 2022 Sep 22. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hoboken, N.J. : Wiley-Blackwell; Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| MeSH Terms: | Epilepsy*/genetics ; Intellectual Disability*/genetics ; Intellectual Disability*/pathology ; Nails, Malformed*/genetics ; Vacuolar Proton-Translocating ATPases*/genetics ; Deafness* ; Nail Diseases*; Humans ; Phenotype ; Seizures ; Syndrome |
| Abstract: | ATP6V1B2 pathogenic variants are linked with variable phenotypes, such as dominant deafness-onychodystrophy syndrome (DDOD), autosomal dominant Zimmermann-Laband syndrome type 2 (ZLS2), and some cases of DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [ID], and seizures). Epilepsy was first linked to ATP6V1B2, when the p.(Glu374Gln) missense variant was detected in a patient with ID and seizures, but without characteristic features of DDOD or ZLS2 syndromes. We herein report a novel pathogenic ATP6V1B2:p.Glu374Gly variant detected in an adult patient with ID and myoclonic-atonic seizures. The (re)occurrence of different variants affecting the same highly conserved hydrophilic glutamic acid on position 374 of the V-proton ATPase subunit B, indicates a potential novel pathogenic hotspot and a critical role for the specific residue in the development of epilepsy. ATP6V1B2 gene defects should be considered when analyzing patients with epilepsy, even in the absence of most cardinal features of DDOD, DOORS, or ZLS such as deafness, onychodystrophy, and osteodystrophy.; (© 2022 Wiley Periodicals LLC.) |
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| Contributed Indexing: | Keywords: ATP6V1B2; WES; epilepsy; neurodevelopmental delay; pathogenic variant |
| Substance Nomenclature: | EC 7.1.2.2 (ATP6V1B2 protein, human); EC 3.6.1.- (Vacuolar Proton-Translocating ATPases) |
| Entry Date(s): | Date Created: 20220922 Date Completed: 20221116 Latest Revision: 20230130 |
| Update Code: | 20260130 |
| DOI: | 10.1002/ajmg.a.62971 |
| PMID: | 36135319 |
| Database: | MEDLINE |
Case Reports; Journal Article