A rare family with Hereditary Spastic Paraplegia Type 35 due to novel FA2H mutations: a case report with literature review

Abstract

Background: Hereditary Spastic Paraplegia Type 35 is a complicated form of HSP characterized by progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Mutations in the fatty acid 2-hydroxylase (FA2H) gene have been associated SPG35.

Methods: Sequencing of FA2H gene was conducted in a Chinese non-consanguineous family with two affected siblings manifesting with typical clinical features of SPG 35. 100 healthy individuals were set for control.

Result: Triple heterozygous mutations in FA2H gene (c.968C>A; c.976G>A; c.688G>A) were identified in the two affected siblings. All the mutations were not documented previously and were not detected among 100 healthy controls.

Conclusion: In this study we identified the first SPG 35 family in Han population. Triple FA2H mutations seem to result in a severe phenotype while more patients are needed to establish the genotype-phenotype correlations.