Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia

作者：Halevy Ayelet^*; Lerer Israela; Cohen Rony; Kornreich Liora; Shuper Avinoam; Gamliel Moria; Zimerman Bat El; Korabi Isam; Meiner Vardiella; Straus**erg Rachel; Lossos Alexander

来源：Journal of Neurology, 2014, 261(11): 2165-2169.

DOI：10.1007/s00415-014-7457-x

• Cerebellar atrophy
• EXOSC3
• HSP
• Pontocerebellar hypoplasia
• PCH
• Spastic paraplegia

We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G > T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy.

• 出版日期2014-11