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. 2015 Jul 9:5:306.
doi: 10.7916/D8D21WQ0. eCollection 2015.

Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome

Mustafa A Salih  1 , Mohammed Z Seidahmed  2 , Heba Y El Khashab  1 , Muddathir H A Hamad  1 , Thomas M Bosley  3 , Sabrina Burn  4 , Angela Myers  5 , Megan L Landsverk  5 , Patricia L Crotwell  5 , Kaya Bilguvar  6 , Shrikant Mane  6 , Michael C Kruer  7
Affiliations

Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome

Mustafa A Salih et al. Tremor Other Hyperkinet Mov (N Y). .

Abstract

Background: The etiology of many cases of childhood-onset chorea remains undetermined, although advances in genomics are revealing both new disease-associated genes and variant phenotypes associated with known genes.

Methods: We report a Saudi family with a neurodegenerative course dominated by progressive chorea and dementia in whom we performed homozygosity mapping and whole exome sequencing.

Results: We identified a homozygous missense mutation in GM2A within a prominent block of homozygosity. This mutation is predicted to impair protein function.

Discussion: Although discovered more than two decades ago, to date, only five patients with this rare form of GM2 gangliosidosis have been reported. The phenotype of previously described GM2A patients has been typified by onset in infancy, profound hypotonia and impaired volitional movement, intractable seizures, hyperacusis, and a macular cherry red spot. Our findings expand the phenotypic spectrum of GM2A mutation-positive gangliosidosis to include generalized chorea without macular findings or hyperacusis and highlight how mutations in neurodegenerative disease genes may present in unexpected ways.

Keywords: Chorea; GM2 gangliosidosis; dementia; neurodegeneration.

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Conflict of interest statement

Conflict of Interest: M.C.K. receives research support from Retrophin, Inc.

Figures

Figure 1
Figure 1. Features of Index Family. (A) Pedigree depicting family structure: Circle represent females, squares depict males. Consanguinity is shown via double lines linking parents. Affected status is denoted by a filled shape. Death is indicated by a slash. (B) Brain magnetic resonance imaging demonstrating generalized cortical atrophy in patient 3.
Figure 2
Figure 2. Clustal Omega cross-species alignment of amino acid residues. The proline at position 55 is conserved throughout eukaryotes.
See this image and copyright information in PMC

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