Tey, Shelisa and Shahrizaila, Nortina and Drew, Alexander P. and Samulong, Sarimah and Goh, Khean Jin and Battaloglu, Esra and Atkinson, Derek and Parman, Yesim and Jordanova, Albena and Chung, Ki Wha and Choi, Byung-Ok and Li, Yi-Chung and Auer-Grumbach, Michaela and Nicholson, Garth A. and Kennerson, Marina L. and Ahmad-Annuar, Azlina (2019) Linkage analysis and whole exome sequencing reveals AHNAK2 as a novel genetic cause for autosomal recessive CMT in a Malaysian family. Neurogenetics, 20 (3). pp. 117-127. ISSN 1364-6745, DOI https://doi.org/10.1007/s10048-019-00576-3.
Full text not available from this repository.Abstract
Charcot-Marie-Tooth (CMT) disease is a form of inherited peripheral neuropathy that affects motor and sensory neurons. To identify the causative gene in a consanguineous family with autosomal recessive CMT (AR-CMT), we employed a combination of linkage analysis and whole exome sequencing. After excluding known AR-CMT genes, genome-wide linkage analysis mapped the disease locus to a 7.48-Mb interval on chromosome 14q32.11–q32.33, flanked by the markers rs2124843 and rs4983409. Whole exome sequencing identified two non-synonymous variants (p.T40P and p.H915Y) in the AHNAK2 gene that segregated with the disease in the family. Pathogenic predictions indicated that p.T40P is the likely causative allele. Analysis of AHNAK2 expression in the AR-CMT patient fibroblasts showed significantly reduced mRNA and protein levels. AHNAK2 binds directly to periaxin which is encoded by the PRX gene, and PRX mutations are associated with another form of AR-CMT (CMT4F). The altered expression of mutant AHNAK2 may disrupt the AHNAK2-PRX interaction in which one of its known functions is to regulate myelination. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | AHNAK2; Autosomal recessive CMT; Inherited neuropathy |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 18 Dec 2019 02:34 |
| Last Modified: | 18 Dec 2019 02:34 |
| URI: | http://eprints.um.edu.my/id/eprint/23250 |
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