TY - JOUR
T1 - Chorea-acanthocytosis
AU - Walker, Susan
AU - Dad, Rubina
AU - Thiruvahindrapuram, Bhooma
AU - Ullah, Muhammed Ikram
AU - Ahmad, Arsalan
AU - Hassan, Muhammad Jawad
AU - Scherer, Stephen W.
AU - Minassian, Berge A.
N1 - Funding Information:
The Article Processing Charge was funded by the authors.
Funding Information:
The authors thank the family for their participation in the study and The Centre for Applied Genomics for their analytical and technical support. This work was supported by The Centre for Applied Genomics, the University of Toronto McLaughlin Centre, Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the Canadian Institute for Advanced Research, and the Canada Foundation for Innovation. R.D. gratefully acknowledges her funding by the Higher Education Commission of Pakistan under the International Research Support Initiative Program (HEC-IRSIP). S.W.S. is funded by the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. B.A.M holds the University of Toronto Michael Bahen Chair in Epilepsy Research and the University of Texas Southwestern Jimmy Elizabeth Westcott Distinguished Chair in Pediatric Neurology.
Funding Information:
This work was supported by The Centre for Applied Genomics, the University of Toronto McLaughlin Centre, Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the Canadian Institute for Advanced Research, and the Canada Foundation for Innovation.
Funding Information:
S. Walker, R. Dad, B. Thiruvahindrapuram, M.I. Ullah, A. Ahmad, and M.J. Hassan report no disclosures. S.W. Scherer holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children; is on the scientific advisory board of Deep Genomics; has served on the scientific advisory board of Population Diagnostics; has served on the editorial boards of Genomic Medicine, Genes, Genomes, Genetics, the Journal of Personalized Medicine, the Open Genomics Journal, the Hugo Journal, Genome Medicine, the Journal of Neurodevelopmental Disorders, Autism Research, PathoGenetics, Comparative and Functional Genomics, BMC Medical Genomics, and Cytogenetics and Genome Research; and has received research support from the Genome Canada/Ontario Genomics Institute, Canadian Institutes of Health Research, Canadian Institute for Advanced Research, McLaughlin Centre, Canada Foundation for Innovation, Government of Ontario, and NIH. B.A. Minassian holds patents for diagnostic testing of the following genes: EPM2A, EPM2B, MECP2, and VMA21; has received research support from the NIH; and has received license fee payments/royalty payments from patents for diagnostic testing of the following genes: EPM2A, EPM2B,
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Objective To determine a molecular diagnosis for a large multigenerational family of South Asian ancestry with seizures, hyperactivity, and episodes of tongue biting. Methods Two affected individuals from the family were analyzed by whole-genome sequencing on the Illumina HiSeq X platform, and rare variants were prioritized for interpretation with respect to the phenotype. Results A previously undescribed, 1-kb homozygous deletion was identified in both individuals sequenced, which spanned 2 exons of the VPS13A gene, and was found to segregate in other family members. Conclusions VPS13A is associated with autosomal recessive chorea-acanthocytosis, a diagnosis consistent with the phenotype observed in this family. Whole-genome sequencing presents a comprehensive and agnostic approach for detecting diagnostic mutations in families with rare neurologic disorders.
AB - Objective To determine a molecular diagnosis for a large multigenerational family of South Asian ancestry with seizures, hyperactivity, and episodes of tongue biting. Methods Two affected individuals from the family were analyzed by whole-genome sequencing on the Illumina HiSeq X platform, and rare variants were prioritized for interpretation with respect to the phenotype. Results A previously undescribed, 1-kb homozygous deletion was identified in both individuals sequenced, which spanned 2 exons of the VPS13A gene, and was found to segregate in other family members. Conclusions VPS13A is associated with autosomal recessive chorea-acanthocytosis, a diagnosis consistent with the phenotype observed in this family. Whole-genome sequencing presents a comprehensive and agnostic approach for detecting diagnostic mutations in families with rare neurologic disorders.
UR - http://www.scopus.com/inward/record.url?scp=85053872979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053872979&partnerID=8YFLogxK
U2 - 10.1212/NXG.0000000000000242
DO - 10.1212/NXG.0000000000000242
M3 - Article
C2 - 29845114
AN - SCOPUS:85053872979
VL - 4
JO - Neurology: Genetics
JF - Neurology: Genetics
SN - 2376-7839
IS - 3
M1 - e242
ER -