Universität zu Köln

Asif, Maria, Mocanu, Ionut Dragos, Abdullah, Uzma, Hoehne, Wolfgang, Altmueller, Janine, Makhdoom, Ehtisham Ul Haq, Thiele, Holger, Baig, Shahid Mahmood, Nuernberg, Peter, Graul-Neumann, Luitgard and Hussain, Muhammad Sajid (2022). A novel missense variant of SCN4A co-segregates with congenital essential tremor in a consanguineous Kurdish family. Am. J. Med. Genet. A, 188 (4). S. 1251 - 1259. HOBOKEN: WILEY. ISSN 1552-4833

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Abstract

Essential tremor (ET) is a neurological disorder characterized by bilateral and symmetric postural, isometric, and kinetic tremors of forelimbs produced during voluntary movements. To date, only a single SCN4A variant has been suggested to cause ET. In continuation of the previous report on the association between SCN4A and ET in a family from Spain, we validated the pathogenicity of a novel SCN4A variant and its involvement in ET in a second family affected by this disease. We recruited a Kurdish family with four affected members manifesting congenital tremor. Using whole-exome sequencing, we identified a novel missense variant in SCN4A, NM_000334.4:c.4679C>T; p.(Pro1560Leu), thus corroborating SCN4A's role in ET. The residue is highly conserved across vertebrates and the substitution is predicted to be pathogenic by various in silico tools. Western blotting and immunocytochemistry performed in cells derived from one of the patients showed reduced immunoreactivity of SCN4A as compared to control cells. The study provides supportive evidence for the role of SCN4A in the etiology of ET and expands the phenotypic spectrum of channelopathies to this neurological disorder.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Asif, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Mocanu, Ionut Dragos UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdullah, Uzma UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoehne, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Makhdoom, Ehtisham Ul Haq UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Baig, Shahid Mahmood UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Graul-Neumann, Luitgard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hussain, Muhammad Sajid UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-599904
DOI:	10.1002/ajmg.a.62610
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	188
Number:	4
Page Range:	S. 1251 - 1259
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHANNEL ALPHA-SUBUNIT; MUTATIONS; DISEASE; GENETICS; GENES Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59990