Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness.

Leukodystrophies are a heterogeneous group of rare inherited disorders that mostly involve the white matter of the CNS. These conditions are characterized by primary glial cell and myelin sheath pathology of variable aetiology, which causes secondary axonal degeneration, generally emerging with disease progression. Whole exome sequencing performed in five large consanguineous nuclear families allowed us to identify homozygosity for two recurrent missense variants affecting highly conserved residues of RNF220 as the causative event underlying a novel form of leukodystrophy with ataxia and sensorineural deafness.

Autism and metabolic diseases.

Autism is an etiologic heterogeneous entity caused by many different diseases occurring in the central nervous system at an early stage in life. Several metabolic defects have been associated with autistic symptoms with a rate higher than that found in the general population. Inborn errors of metabolism can probably account for less than 5% of individuals.