Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy.

Neurogenetics 11(3):319-25 (2010) PMID 20082205

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.