Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities

J Pathol. 2011 Sep;225(1):12-8. doi: 10.1002/path.2941.


Linkage analysis with subsequent candidate gene sequencing is typically used to diagnose novel inherited syndromes. It is now possible to expedite diagnosis through the sequencing of all coding regions of the genome (the exome) or full genomes. We sequenced the exomes of four members of a family presenting with spondylo-epiphyseal dysplasia and retinitis pigmentosa and identified a six-base-pair (6-bp) deletion in GNPTG, the gene implicated in mucolipidosis type IIIγ. The diagnosis was confirmed by biochemical studies and both broadens the mucolipidosis type III phenotype and demonstrates the clinical utility of next-generation sequencing to diagnose rare genetic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping / methods
  • Computational Biology / methods
  • DNA Mutational Analysis / methods
  • Female
  • Gene Deletion
  • Genetic Linkage
  • Glycoside Hydrolases / blood
  • Heterozygote
  • Humans
  • Male
  • Mucolipidoses / diagnosis*
  • Mucolipidoses / enzymology
  • Mucolipidoses / genetics
  • Mutation
  • Osteochondrodysplasias / diagnosis*
  • Osteochondrodysplasias / enzymology
  • Osteochondrodysplasias / genetics
  • Pedigree
  • Rare Diseases / diagnosis
  • Rare Diseases / enzymology
  • Rare Diseases / genetics
  • Retinitis Pigmentosa / diagnosis*
  • Retinitis Pigmentosa / enzymology
  • Retinitis Pigmentosa / genetics
  • Transferases (Other Substituted Phosphate Groups) / genetics


  • Transferases (Other Substituted Phosphate Groups)
  • GNPTG protein, human
  • Glycoside Hydrolases