Type

Journal Article

Authors

Sean Ennis
Sallyann Lynch
Orla Walsh
Cara McDonagh
Dara McCreary
Christine Albertyn
Blathnaid McCoy
Sinead M Murphy
David Webb
Raymond Murphy
and 2 others

Subjects

Biochemistry

Topics
child preschool male mutation missense cytoskeletal proteins young adult exome ireland middle aged child lod score sequence analysis dna genetic loci ataxia inositol 1 4 5 trisphosphate receptors itpr1 protein human polymorphism single nucleotide pedigree humans adult adolescent chromosomes human pair 13 calmodulin binding proteins female ubr4 protein human genetics diagnosis

A novel locus for episodic ataxia:UBR4 the likely candidate. (2013)

Abstract Episodic ataxias (EAs) are rare neurological channelopathies that are characterized by spells of imbalance and a lack of co-ordination. There are seven clinically recognized EAs and multiple isolated cases. Five disease-causing genes have been identified to date. We describe a novel form of autosomal dominant EA in a large three-generation Irish family. This form of EA presents in early childhood with periods of unsteadiness generalized weakness and slurred speech during an attack, which may be triggered by physical tiredness or stress. Linkage analysis undertaken in 13 related individuals identified a single disease locus (1p36.13-p34.3) with a LOD score of 3.29. Exome sequencing was performed. Following data analysis, which included presence/absence within the linkage peak, two candidate variants were identified. These are located in the HSPG2 and UBR4 genes. UBR4 is an ubiquitin ligase protein that is known to interact with calmodulin, a Ca(2+) protein, in the cytoplasm. It also co-localizes with ITPR1 a calcium release channel that is a major determinant of mammal co-ordination. Although UBR4 is not an ion channel gene, the potential for disrupted Ca(2+) control within neuronal cells highlights its potential for a role in this form of EA.
Collections Ireland -> IT Tallaght -> PubMed

Full list of authors on original publication

Sean Ennis, Sallyann Lynch, Orla Walsh, Cara McDonagh, Dara McCreary, Christine Albertyn, Blathnaid McCoy, Sinead M Murphy, David Webb, Raymond Murphy and 2 others

Experts in our system

1
Sean Ennis
University College Dublin
Total Publications: 52
 
2
Sinead Murphy
IT Tallaght
Total Publications: 32
 
3
David Webb
University College Dublin
Total Publications: 8
 
4
R P Murphy
Trinity College Dublin
Total Publications: 32