A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation

Changrui Xiao; Elaine M Binkley; Jessica Rexach; Amy Knight-Johnson; Pravin Khemani; Brent L Fogel; Soma Das; Edwin M Stone; Christopher M Gomez

doi:10.1212/NXG.0000000000000357

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A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation

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A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation

Changrui Xiao, Elaine M Binkley, Jessica Rexach, Amy Knight-Johnson, Pravin Khemani, Brent L Fogel, Soma Das, Edwin M Stone and Christopher M Gomez

Neurology. Genetics, Vol.5(5), pp.e357-e357

10/2019

DOI: 10.1212/NXG.0000000000000357

PMCID: PMC6812731

PMID: 31750392

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Abstract

To identify the genetic cause of autosomal dominant spinocerebellar ataxia and retinitis pigmentosa in a large extended pedigree. Clinical studies were done at 4 referral centers. Ten individuals in the same extended family participated in at least a portion of the study. Records were obtained from an 11th, deceased, individual. Neurologic and dermatological examinations were performed. Ophthalmologic evaluation including funduscopic examination and in some cases ocular coherence tomography were used to identify the presence of retinal disease. Whole exome sequencing (WES), in conjunction with Sanger sequencing and segregation analysis, was used to identify potential genetic mutation. Affected individuals reported slowly progressive cerebellar ataxia with age at onset between 38 and 57. Imaging demonstrated cerebellar atrophy (3/3). WES identified a novel heterozygous mutation in the elongation of very long chain fatty acids 4 ( ) gene (c.512T>C, p.Ile171Thr) that segregated with ataxia in 7 members tested. Four of 8 members who underwent ophthalmologic evaluation were found to have retinitis pigmentosa. No skin findings were identified or reported. Ocular movement abnormalities and pyramidal tract signs were also present with incomplete penetrance. We report a family with both spinocerebellar ataxia and retinal dystrophy associated with an mutation. In addition, to supporting prior reports that mutations can cause spinocerebellar ataxia, our findings further broaden the spectrum of clinical presentations associated with spinocerebellar ataxia 34.

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Title: Subtitle: A family with spinocerebellar ataxia and retinitis pigmentosa attributed to an ELOVL4 mutation
Creators: Changrui Xiao - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Elaine M Binkley - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Jessica Rexach - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Amy Knight-Johnson - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Pravin Khemani - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Brent L Fogel - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Soma Das - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Edwin M Stone - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Christopher M Gomez - National Human Genome Research Institute (C.X.), Bethesda, MD; Department of Neurology (C.M.G.), University of Chicago Hospitals, IL; Department of Ophthalmology and Visual Sciences (E.M.B., E.M.S.), University of Iowa; Department Neurology (J.R., B.L.F.), David Geffen School of Medicine, University of California Los Angeles; Department of Genetics (A.K.-J., S.D.), University of Chicago, IL; and Department of Neurology (P.K.), UTSW Medical Center, Dallas, TX
Resource Type: Journal article
Publication Details: Neurology. Genetics, Vol.5(5), pp.e357-e357
DOI: 10.1212/NXG.0000000000000357
PMID: 31750392
PMCID: PMC6812731
NLM abbreviation: Neurol Genet
ISSN: 2376-7839
eISSN: 2376-7839
Publisher: United States
Grant note: K08 NS105916 / NINDS NIH HHS
Language: English
Date published: 10/2019
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Ophthalmology and Visual Sciences
Record Identifier: 9984070330502771

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