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UBQLN2 mutation causing heterogeneous X‐linked dominant neurodegeneration
Author(s) -
Fahed Akl C.,
McDonough Barbara,
Gouvion Cynthia M.,
Newell Kathy L.,
Dure Leon S.,
Bebin Martina,
Bick Alexander G.,
Seidman Jonathan G.,
Harter Donald H.,
Seidman Christine E.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24164
Subject(s) - dysarthria , amyotrophic lateral sclerosis , neurodegeneration , dementia , exome sequencing , mutation , phenocopy , genetics , frontotemporal dementia , biology , phenotype , dysphagia , disease , neuroscience , medicine , gene , pathology , audiology , surgery
We report a 5‐generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67‐year‐old woman with amyotrophic lateral sclerosis. Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin‐2 gene ( UBQLN2 ) with X‐linked inheritance in all studied affected individuals. As ubiquilin‐2–positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations. ANN NEUROL 2014;75:793–798