Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy
Roula Ghaoui, Johanna Palmio, Janice Brewer, Monkol Lek, Merrilee Needham, Anni Evila, Peter Hackman, Per-Harald Jonson, Sini Penttila, Anna Vihola, Sanna Huovinen, Mikaela Lindfors, Ryan L Davis, Leigh Waddell, Simran Kaur, Con Yiannikas, Kathryn North, Nigel Clarke, Daniel G MacArthur, Carolyn M Sue Show all
NEUROLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2016
OBJECTIVE: To report novel disease and pathology due to HSPB8 mutations in 2 families with autosomal dominant distal neuromuscular disease showing both myofibrillar and rimmed vacuolar myopathy together with neurogenic changes. METHODS: We performed whole-exome sequencing (WES) in tandem with linkage analysis and candidate gene approach as well as targeted next-generation sequencing (tNGS) to identify causative mutations in 2 families with dominant rimmed vacuolar myopathy and a motor neuropathy. Pathogenic variants and familial segregation were confirmed using Sanger sequencing. RESULTS: WES and tNGS identified a heterozygous change in HSPB8 in both families: c.421A > G p.K141E in family 1 ..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by National Human Genome Research Institute of the NIH
Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE
This project was supported by Australian National Health and Medical Research Council (NHMRC) grants: APP1074954 (R. Ghaoui), APP1031893 and APP1022707 (K.N. North and N.F. Clarke), APP1035828 (N.F. Clarke), APP1008433 (C.M. Sue), APP1037797 (R.L. Davis), and Muscular Dystrophy New South Wales (R. Ghaoui). Exome sequencing was supported by grants from the National Human Genome Research Institute of the NIH (Medical Sequencing Program grant U54 HG003067 to the Broad Institute principal investigator, E. Lander). Also supported by Juselius Foundation, Finnish Academy, and the Folkhalsan Foundation (B. Udd).