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

Kasmintan A Schrader, Alireza Heravi-Moussavi, Paula J Waters, Janine Senz, James Whelan, Gavin Ha, Patrice Eydoux, Torsten Nielsen, Barry Gallagher, Arusha Oloumi, Niki Boyd, Bridget A Fernandez, Terry-Lynn Young, Steven Jm Jones, Martin Hirst, Sohrab P Shah, Marco A Marra, Jane Green, David G Huntsman, The Journal of pathology 225, 12-8 (2011)
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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 III╬│. 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.