Search

Hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper motor neuron disorders. Although the primary feature of HSP is lower extremity weakness ("uncomplicated" form), sequelae and clinical features of this disorder may include other neurological deficits such as dementia, neuropathy, retinopathy, mental retardation, and seizures ("complicated" form). To date, more than 56 different genetic loci and 41 HSP-related genes have been described as causative for autosomal dominant, recessive or X-linked HSP. One such locus on chromosome 15q, also known as locus SPG11 (OMIM 604360), has been shown to link to a complicated autosomal recessive form of disease known as HSP with thin corpus callosum (HSP-TCC). Herein we describe the identification and clinical presentation of a new family from Eastern Turkey with autosomal recessive HSP associated with mental retardation, epilepsy and a thinned corpus callosum on MRI. Using array-based SNP genotyping, we demonstrate linkage to the SPG11 locus on chromosome 15q13-15. Array-based copy number variation (CNV) analysis was also performed. Our results not only expand the phenotypic heterogeneity associated with the SPG11 locus to include an earlier age of onset with epilepsy, but also confirm the linkage to a 13 Mbp interval on chromosome 15q. This data, when added to those previously reported, support the notion that SPG11 is a phenotypically and genetically heterogeneous disorder. [ABSTRACT FROM AUTHOR]