Mutations in VLDLR as a Cause for Autosomal Recessive Cerebellar Ataxia With Mental Retardation (Dysequilibrium Syndrome)

Author:

Boycott Kym M.1,Bonnemann Carsten2,Herz Joachim3,Neuert Stephanie4,Beaulieu Chandree4,Scott James N.5,Venkatasubramanian Anuradha2,Parboosingh Jillian S.4

Affiliation:

1. Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada,

2. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia

3. University of Texas Southwestern Medical Center, Dallas, Texas

4. Department of Medical Genetics, University of Calgary, Calgary, Canada

5. Department of Radiology, Foothills Hospital, Calgary, Canada

Abstract

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. Here, we report the first patient heterozygous for 2 novel mutations in VLDLR. An 18-month-old girl presented with significant hypotonia, global developmental delay, and truncal and peripheral ataxia. Magnetic resonance imaging of the brain demonstrated hypoplasia of the inferior cerebellar vermis and hemispheres, small pons, and a simplified cortical sulcation pattern. Sequence analysis of the VLDLR gene identified a nonsense and missense mutation. Six mutations in VLDLR have now been identified in 5 families with a phenotype characterized by moderate-to-profound mental retardation, delayed ambulation, truncal and peripheral ataxia, and occasional seizures. Neuroanatomically, the loss-of-function effect of the different mutations is indistinguishable. VLDLR-associated cerebellar hypoplasia is emerging as a panethnic, clinically, and molecularly well-defined genetic syndrome.

Publisher

SAGE Publications

Subject

Clinical Neurology,Pediatrics, Perinatology, and Child Health

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