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

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 gene mutations. Currently there are more than 60 reported 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 gene mutation.

RESULTS

Most HSPs-SPG3A patients exhibited an early age at onset (AAO) of <10 years old, and showed an autosomal dominant pure spastic paraplegia. We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes, with distal atrophy being the most common complicated symptom. The AAO of each mutation group was not statistically significant ( > 0.05). The mutational spectrum associated with gene mutation is wide, and most mutations are missense mutations, but do not involve the functional motif of 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 gene.