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Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein
CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-g...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454856/ https://www.ncbi.nlm.nih.gov/pubmed/37628707 http://dx.doi.org/10.3390/genes14081656 |
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author | Mori, Takuma Zhou, Mengyun Tabuchi, Katsuhiko |
author_facet | Mori, Takuma Zhou, Mengyun Tabuchi, Katsuhiko |
author_sort | Mori, Takuma |
collection | PubMed |
description | CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK-related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK-related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK-related disorders, allow us to understand the pathophysiology of CASK-related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK-related disorders. |
format | Online Article Text |
id | pubmed-10454856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104548562023-08-26 Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein Mori, Takuma Zhou, Mengyun Tabuchi, Katsuhiko Genes (Basel) Review CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with CASK-related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of CASK-related disorders, research groups have employed diverse methods, including the generation of CASK knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate CASK mutant mice carrying missense mutations from patients with CASK-related disorders, allow us to understand the pathophysiology of CASK-related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of CASK-related disorders. MDPI 2023-08-20 /pmc/articles/PMC10454856/ /pubmed/37628707 http://dx.doi.org/10.3390/genes14081656 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mori, Takuma Zhou, Mengyun Tabuchi, Katsuhiko Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title | Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title_full | Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title_fullStr | Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title_full_unstemmed | Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title_short | Diverse Clinical Phenotypes of CASK-Related Disorders and Multiple Functional Domains of CASK Protein |
title_sort | diverse clinical phenotypes of cask-related disorders and multiple functional domains of cask protein |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454856/ https://www.ncbi.nlm.nih.gov/pubmed/37628707 http://dx.doi.org/10.3390/genes14081656 |
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