Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in the deoxyguanosine gene using array-based comparative genomic hybridisation
Journal
Archives of Disease in Childhood
Journal Volume
94
Journal Issue
1
Pages
55-58
Date Issued
2009
Author(s)
Abstract
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.
SDGs
Other Subjects
deoxyguanosine; mitochondrial DNA; oligonucleotide; article; blood; case report; comparative genomic hybridization; deoxyguanosine gene; diagnostic procedure; disorders of mitochondrial functions; DNA determination; DNA microarray; DNA sequence; DNA synthesis; exon; gene; gene mutation; heterozygosity; human; infant; liver; liver failure; male; missense mutation; mitochondrial DNA depletion; newborn screening; priority journal; retrospective study; tyrosinemia; Alanine; Base Sequence; Deoxyguanine Nucleotides; DNA Mutational Analysis; DNA, Mitochondrial; Exons; Gene Deletion; Heterozygote Detection; Humans; Infant; Infant, Newborn; Liver Failure; Male; Mitochondrial Diseases; Molecular Sequence Data; Mutation, Missense; Oligonucleotide Array Sequence Analysis; Tandem Mass Spectrometry; Treatment Outcome; Tyrosine
Type
journal article