Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies
| Autor: | Karen W. Gripp, Ingrid M. Wentzensen, Julie D. Kaplan, Lindsay B. Henderson, Germaine Pierre, Maggie Williams, Anne McRae, Kerstin Kutsche, Jean-Marc Good, Julia Baptista, Marleen Simon, Anirban Majumdar, Mary Beth Dinulos, Andrea Superti-Furga, Ellen van Binsbergen, Lisette Leeuwen, Ingrid Scurr, Sarah F. Smithson, Heather M. McLaughlin |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Hypertrichosis Potassium Channels Adolescent Small-Conductance Calcium-Activated Potassium Channels Nails Malformed Biology Article Craniofacial Abnormalities 03 medical and health sciences Epilepsy 0302 clinical medicine Intellectual Disability Genetics research Intellectual disability Genetics medicine Humans Missense mutation Abnormalities Multiple Child Gene Genetics (clinical) Fibromatosis Gingival Abnormalities Multiple/genetics Abnormalities Multiple/pathology Channelopathies/genetics Channelopathies/pathology Craniofacial Abnormalities/genetics Craniofacial Abnormalities/pathology Ether-A-Go-Go Potassium Channels/genetics Female Fibromatosis Gingival/genetics Fibromatosis Gingival/pathology Gain of Function Mutation Hallux/abnormalities Hallux/pathology Hand Deformities Congenital/genetics Hand Deformities Congenital/pathology Intellectual Disability/genetics Intellectual Disability/pathology Nails Malformed/genetics Nails Malformed/pathology Phenotype Potassium Channels/genetics Small-Conductance Calcium-Activated Potassium Channels/genetics Thumb/abnormalities Thumb/pathology Coarse facial features medicine.disease Ether-A-Go-Go Potassium Channels Paediatric neurological disorders 030104 developmental biology Thumb KCNK4 Hallux Channelopathies Hand Deformities Congenital 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Human Genetics, 29, 1384-1395. Nature Publishing Group European journal of human genetics, vol. 29, no. 9, pp. 1384-1395 European Journal of Human Genetics |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-021-00818-9 |
| Popis: | Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann–Laband and Temple–Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3. |
| Databáze: | OpenAIRE |
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