TY - JOUR
T1 - Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (Dysequilibrium syndrome)
AU - Boycott, Kym M.
AU - Bonnemann, Carsten
AU - Herz, Joachim
AU - Neuert, Stephanie
AU - Beaulieu, Chandree
AU - Scott, James N.
AU - Venkatasubramanian, Anuradha
AU - Parboosingh, Jillian S.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Cerebellar hypoplasia
KW - Dysequilibrium syndrome
KW - VLDLR
UR - http://www.scopus.com/inward/record.url?scp=74949091198&partnerID=8YFLogxK
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U2 - 10.1177/0883073809332696
DO - 10.1177/0883073809332696
M3 - Article
C2 - 19332571
AN - SCOPUS:74949091198
SN - 0883-0738
VL - 24
SP - 1310
EP - 1315
JO - Journal of child neurology
JF - Journal of child neurology
IS - 10
ER -