SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia.
Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. Snickers@adhb.govt.nz.
Sarah L
SL
Nickerson
Centre for Translational Pathology, University of Melbourne, Corner Grattan Street and Royal Parade, Parkville, Victoria 3010, Australia. Renate.mn@gmail.com.
Renate
R
Marquis-Nicholson
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. KClaxton@adhb.govt.nz.
Karen
K
Claxton
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. FernA@adhb.govt.nz.
Fern
F
Ashton
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. IvoneL@adhb.govt.nz.
Ivone U S
IU
Leong
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. DProsser@adhb.govt.nz.
Debra O
DO
Prosser
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. JLove@adhb.govt.nz.
Jennifer M
JM
Love
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. AliceG@adhb.govt.nz.
Alice M
AM
George
Centre for Translational Pathology, University of Melbourne, Corner Grattan Street and Royal Parade, Parkville, Victoria 3010, Australia. graham.taylor@unimelb.edu.au.
Graham
G
Taylor
Paediatric Metabolic Service, Starship Children's Hospital, Auckland 1148, New Zealand. callumw@adhb.govt.nz.
Callum
C
Wilson
Clinical Genetics Group, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand. macgardner@gmail.com.
R J McKinlay
RJ
Gardner
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand. DonaldL@adhb.govt.nz.
Donald R
DR
Love
ARSACS; SACS; autosomal recessive ataxia; consanguinity; exome sequencing; homozygosity; microarray; sacsin