Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations

摘要: Background In the clinically and genetically heterogeneous group of hereditary spastic paraplegias (HSPs), mutations in SPAST gene are most frequently found cause a pure autosomal dominant form. Objective To provide clinical genetic characteristics Dutch patients with HSP due to mutation (SPG4). Methods carriers were identified through comprehensive national database search. Available medical records reviewed. Results 151 carried 60 different changes gene, which one was known polymorphism, 27 novel. Missense (39%). Clinical information available from 72 carriers. Age at onset ranged 1 63 years bimodal peak distribution first decade above age 30. The predominantly paraplegia accompanied by deep sensory disturbances sphincter problems almost 50%. An additional hand tremor 10%. Patients missense exon deletions did not reveal distinctive phenotype. Conclusions show broad spectrum, novel present series. A an accompanying as peculiar feature SPG4. pathogenicity S44L, 4 mutation, possible recessive mode inheritance discussed.