Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome.
Mutations in the polymerase γ (POLG) gene are among the most common causes of mitochondrial disease and more than 160 POLG mutations have been reported. However, a large proportion of patients suspected of having POLG mutations only have one (heterozygous) definitive pathogenic mutation identified. Using oligonucleotide array CGH, we identified a compound heterozygous large intragenic deletion encompassing exons 15-21 of this gene in a child with Alpers syndrome due to mtDNA depletion. This is the first large POLG deletion reported and the findings show the clinical utility of using array CGH in cases where a single heterozygous mutation has been identified in POLG.
Compton
Alison G
AG
Murdoch Childrens Research Institute and Genetic Health Services Victoria, Royal Children's Hospital, Melbourne, Australia.
Troedson
Christopher
C
Wilson
Meredith
M
Procopis
Peter G
PG
Li
Fang-Yuan
FY
Brundage
Ellen K
EK
Yamazaki
Taro
T
Thorburn
David R
DR
Wong
Lee-Jun C
LJ
D002675:Child, Preschool; D055028:Comparative Genomic Hybridization / Q000379:methods*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human