Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in the deoxyguanosine gene using array-based comparative genomic hybridisation

N. C. Lee, D. Dimmock, W. L. Hwu, L. Y. Tang, W. C. Huang, A. C. Chinault, L. J.C. Wong

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

Intragenic exonic deletions, which cannot be detected by direct DNA sequencing, are a common cause of Mendelian disease. Array-based comparative genomic hybridisation (aCGH) is now widely used for the clinical diagnosis of large chromosomal deletions, but not small deletions or analysis of the mitochondrial genome. An oligonucleotide-based microarray that provides highdensity coverage of the entire mitochondrial genome and nuclear genes related to mitochondrial disorders has been developed. In this report, the case of an infant referred with tyrosinaemia on newborn screening who developed liver failure is presented. DNA sequencing revealed a heterozygous missense mutation (c.679G>A, p. E227K) in the deoxyguanosine gene (DGUOK). Oligonucleotide aCGH allowed simultaneous detection of an intragenic heterozygous deletion of exon 4 of DGUOK and mitochondrial DNA depletion in blood and liver. Screening of the parents' DNA samples indicated that the patient was compound heterozygous for these mutations. An older sibling who had died from liver failure was then retrospectively diagnosed with the same mutations. This report shows the clinical utility of this oligoarray in the detection of changes in DNA copy number in both the mitochondrial and nuclear genomes, thus greatly improving the molecular diagnosis of mitochondrial disorders caused by nuclear genes involved in mitochondrial DNA biosynthesis.

原文英語
頁(從 - 到)55-58
頁數4
期刊Archives of Disease in Childhood
94
發行號1
DOIs
出版狀態已發佈 - 一月 1 2009
對外發佈Yes

指紋

Deoxyguanosine
Comparative Genomic Hybridization
Mitochondrial Genome
Mitochondrial DNA
Exons
Mitochondrial Diseases
Liver Failure
Oligonucleotide Array Sequence Analysis
DNA Sequence Analysis
DNA Copy Number Variations
Tyrosinemias
Genes
Mutation
Missense Mutation
Siblings
Parents
Newborn Infant
Liver
DNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

引用此文

Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in the deoxyguanosine gene using array-based comparative genomic hybridisation. / Lee, N. C.; Dimmock, D.; Hwu, W. L.; Tang, L. Y.; Huang, W. C.; Chinault, A. C.; Wong, L. J.C.

於: Archives of Disease in Childhood, 卷 94, 編號 1, 01.01.2009, p. 55-58.

研究成果: 雜誌貢獻文章

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