Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

Abstract

Abstract Background The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders. Approximately 10% of the autosomal dominant (AD) HSPs (ADHSPs) have the spastic paraplegia 3A (SPG3A) genotype which is caused by ATL1 gene mutations. Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear. The study aims to investigate the genotype-phenotype correlation in SPG3A patients. Methods We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation. Results Most HSPs-SPG3A patients exhibited an early age at onset (AAO) of 0.05). The mutational spectrum associated with ATL1 gene mutation is wide, and most mutations are missense mutations, but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein. Conclusions Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients. We also find that exons 4, 7, 8 and 12 are mutation hotspots in ATL1 gene.

Keywords

• Hereditary spastic paraplegia
• SPG3A
• Age at onset
• ATL1
• Mutation
• Genotype-phenotype correlation