title: Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kasmintan A
authors.initials: KA
authors.lastname: Schrader
authors.forename: Alireza
authors.initials: A
authors.lastname: Heravi-Moussavi
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Waters
authors.forename: Janine
authors.initials: J
authors.lastname: Senz
authors.forename: James
authors.initials: J
authors.lastname: Whelan
authors.forename: Gavin
authors.initials: G
authors.lastname: Ha
authors.forename: Patrice
authors.initials: P
authors.lastname: Eydoux
authors.forename: Torsten
authors.initials: T
authors.lastname: Nielsen
authors.forename: Barry
authors.initials: B
authors.lastname: Gallagher
authors.forename: Arusha
authors.initials: A
authors.lastname: Oloumi
authors.forename: Niki
authors.initials: N
authors.lastname: Boyd
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.forename: Terry-Lynn
authors.initials: TL
authors.lastname: Young
authors.forename: Steven Jm
authors.initials: SJ
authors.lastname: Jones
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.forename: Sohrab P
authors.initials: SP
authors.lastname: Shah
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Jane
authors.initials: J
authors.lastname: Green
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
mesh_terms: D000328:Adult; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D006026:Glycoside Hydrolases / Q000097:blood; D006579:Heterozygote; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D010375:Pedigree; D035583:Rare Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics
chemical_list: D017855:Transferases (Other Substituted Phosphate Groups); C504791:GNPTG protein, human; D006026:Glycoside Hydrolases