The analyses of human MCPH1 DNA repair machinery and genetic variations
Abstract: Causal mutations in the MCPH1 gene have been associated with disorders like microcephaly, and recently congenital hearing impairment. This study examined the MCPH1 DNA repair machinery and identified genetic variations of interest in gnomAD database to discuss the biological roles and effects of rare variants in MCPH1-related diseases. Notably, MCPH1 coordinates two of the seven known mechanisms of DNA repair which confirmed its roles in neurogenesis and chromatin condensation. A pathogenic missense variant in MCPH1 p.Gly753Arg, and two pathogenic frameshifts MCPH1 p.Asn189LysfsTer15 and p.Cys624Ter identified in this study, already had entries in ClinVar and were associated with microcephaly. A pathogenic frameshift in MCPH1 p.Val10SerfsTer5 with a loss-of-function flag and a pathogenic stop gained p.Ser571Ter variants with ultra-rare allele frequency (MAF ≤ 0.001) were identified but have not been linked to any phenotype. The predicted pathogenic ultra-rare variants identified in this study, warranty phenotypic discovery, and also positioned these variants or nearby deleterious variants candidate for screening in MCPH1-associated rare diseases.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
The analyses of human MCPH1 DNA repair machinery and genetic variations ; volume:19 ; number:1 ; year:2024 ; extent:9
Open medicine ; 19, Heft 1 (2024) (gesamt 9)
- Creator
-
Oluwole, Oluwafemi G.
- DOI
-
10.1515/med-2024-0917
- URN
-
urn:nbn:de:101:1-2024030113181819801256
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:52 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Oluwole, Oluwafemi G.