Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome

Tremor and Other Hyperkinetic Movements

article

Mustafa A. Salih¹  Mohammed Z. Seidahmed²  Heba Y. El Khashab¹  Muddathir H. A. Hamad¹  Thomas M. Bosley³  Sabrina Burn⁴  Angela Myers⁴  Megan L. Landsverk⁴  Patricia L. Crotwell⁴  Kaya Bilguvar⁶  Shrikant Mane⁶  Michael C. Kruer⁴ 

[1] Division of Pediatric Neurology, College of Medicine, King Saud University;Department of Pediatrics, Security Forces Hospital;Department of Ophthalmology, College of Medicine, King Saud University;Division of Medical Genetics, Sanford Children’s Hospital;Sanford Children’s Health Research Center, Sanford Research Sioux Falls;Department of Genetics, Yale School of Medicine, Yale Center for Genome Analysis;Sanford Neurogenetics & Neurometabolic Disorders Clinic and Pediatric Movement Disorders Clinic, Division of Pediatric Neurology, Sanford Children’s Specialty Clinic Sioux Falls;Departments of Pediatrics & Neurosciences, Sanford College of Medicine, University of South Dakota;Department of Chemistry & Biochemistry, South Dakota State University;University of Arizona College of Medicine, Department of Child Health;Barrow Neurological Institute and Ronald A. Matricaria Institute for Molecular Medicine, Phoenix Children’s Hospital

关键词: Chorea;    dementia;    neurodegeneration;    GM2 gangliosidosis;   

DOI  :  10.5334/tohm.246

学科分类：社会科学、人文和艺术（综合）

来源: Ubiquity Press

【 摘 要 】

Background: The etiology of many cases of childhood-onset chorea remains undetermined, although advances in genomics are revealing both new diseaseassociated 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.

【 授权许可】

CC BY