Exome sequencing reveals two FA2H mutations in a family with a complicated form of Hereditary Spastic Paraplegia and psychiatric impairments

Autosomal recessive spastic paraplegia form 35 (SPG35) is a rare form of Hereditary Spastic Paraplegia (HSP, MIM 18260) characterized by childhood onset of spasticity, cognitive decline and leukodystrophy. Additional clinical features such as seizures, dysphagia, dysarthria, dystonia, neuropathy and brain iron accumulation were also observed. Mutations in the fatty acid 2-hydroxylase (FA2H) gene have been associated to the SPG35 form. FA2H encodes a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent monooxygenase, involved in the synthesis of 2-hydroxy fatty acid galactolipids, that are the major component of myelin sheath . In the current study we report two siblings with a complicated form of hereditary spastic paraparesis carrying two deleterious FA2H compound heterozygous missense mutations identified by exome sequencing.