A novel mutation in the proteolytic domain of LONP1 causes atypical CODAS syndrome

Cerebral, ocular, dental, auricular, skeletal (codas) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in lonp1. it is characterized by intellectual disability, cataracts, delayed tooth eruption, malformed auricles and skeletal abnormalities. we performed whole-exome sequencing on a 12-year-old japanese male with severe intellectual disability, congenital bilateral cataracts, spasticity, hypotonia with motor regression and progressive cerebellar atrophy with hyperintensity of the cerebellar cortex on t2-weighted images. we detected compound heterozygous mutation in lonp1. one allele contained a paternally inherited frameshift mutation (p.ser100glnfs*46). the other allele contained a maternally inherited missense mutation (p.arg786trp), which was predicted to be pathogenic by web-based prediction tools. the two mutations were not found in exome variant server or our 575 in-house control exomes. some features were not consistent with codas syndrome but overlapped with marinesco–sjögren syndrome, a multisystem disorder caused by a mutation in sil1. an atypical mutation site may result in atypical presentation of the lonp1 mutation.