A novel p.Ala34Val variant in C19orf12 is associated with neurodegeneration with brain iron accumulation

Abstract

Loss-of-function mutations in the C19orf12 gene may lead to mitochondrial membrane protein- associated neurodegeneration (MPAN), which is a subtype of neurodegeneration with brain iron accumulation disorders. It is manifest with juvenile-onset spastic paraparesis, dystonia, dysphagia, optic atrophy, decreased cognitive functions, and neuropsychiatric symptoms. Large amounts of iron are accumulated in the globus pallidus and substantia nigra pars reticulata due to abnormal brain iron metabolism. We report a novel C19orf12 (c.101C>T;p.Ala34Val) homozygous mutation in a Turkish man who presented with postural instability, slow gait and anxiety. Neuroimaging showed mild iron deposition in the basal ganglia and cortical atrophy. These results are consistent with the MPAN. This report demonstrates the importance of testing patients with spastic paraplegia, parkinsonism, motor axonal neuropathy, difficulty walking or dysarthria for MPAN.