Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in the deoxyguanosine gene using array-based comparative genomic hybridisation
- 1Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- 2Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- 4Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Professor L-J C Wong, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB2015, Houston, TX 77030, USA;
- Accepted 21 June 2008
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 high-density 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.
See Perspective, p 3
N-C Lee and D Dimmock are joint first authors
Competing interests: None.
Patient consent: Parental consent obtained.