Recurrent null mutation in SPG20 leads to Troyer syndrome.

Troyer syndrome is an autosomal recessive form of complex hereditary spastic paraplegia. To date, the disorder has only been described in the Amish and in kindred from Oman. In Amish, all affected individuals have a homozygous one nucleotide deletion; c.1110delA. In the Omani kindred, all affected have a homozygous two nucleotides deletion; c.364_365delTA (p.Met122ValfsTer2). Here we report the results of homozygosity mapping and whole exome sequencing in two siblings of a consanguineous Turkish family with mild intellectual disability, spastic paraplegia, and muscular dystrophy. We identified the same deletion that has been identified in the Omani kindred, but haplotype analysis suggests a recurrent event, and not a founder mutation. We summarize current knowledge of Troyer syndrome, and propose wider use of whole exome sequencing in routine diagnostics. This applies in particular to nonspecific phenotypes with high heterogeneity, such as spastic paraplegia, intellectual disability, and muscular dystrophy, since in such cases the assignment of a definite diagnosis is frequently delayed.