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

J Hum Genet. 2017 Jun;62(6):653-655. doi: 10.1038/jhg.2017.11. Epub 2017 Feb 2.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • ATP-Dependent Proteases / genetics*
  • Child
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / physiopathology
  • Exome / genetics
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / physiopathology
  • Frameshift Mutation / genetics
  • Genetic Predisposition to Disease
  • Growth Disorders / genetics*
  • Growth Disorders / physiopathology
  • Hip Dislocation, Congenital / genetics*
  • Hip Dislocation, Congenital / physiopathology
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Mitochondrial Proteins / genetics*
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / physiopathology
  • Protein Domains / genetics
  • Spinocerebellar Degenerations / genetics*
  • Spinocerebellar Degenerations / physiopathology
  • Tooth Abnormalities / genetics*
  • Tooth Abnormalities / physiopathology

Substances

  • Mitochondrial Proteins
  • ATP-Dependent Proteases
  • LONP1 protein, human

Supplementary concepts

  • CODAS syndrome