title: Microarray analysis unmasked paternal uniparental disomy of chromosome 12 in a patient with isolated sulfite oxidase deficiency.
abstract: BACKGROUND
  In the investigation of a proband with a biochemical diagnosis of isolated sulfite oxidase deficiency, we identified a homozygous nonsense mutation of the SUOX gene in the proband. However, the mutation was only detected in the father and not the mother. Deletion of the SUOX gene of the mother and paternal disomy of chromosome 12, where the SUOX gene is located, were suspected in view that allele dropout of the mother non-amplified wild-type allele is unlikely.
  
  
  METHODS
  To distinguish the two possible causes, we performed a genome wide microarray analysis in the patient and parents using high-density single-nucleotide microarrays. Whole genome allele sharing of the genomes of the patient and parents were performed by dChip.
  
  
  RESULTS
  In the proband, the whole genome scan showed loss of heterozygosity (LOH) of the entire chromosome 12. However, the LOH is copy neutral and deletion of the SUOX gene of the mother was thus excluded. On whole genome allele sharing analysis, the proband showed a high degree of allele sharing with the father and a very low allele sharing with the mother only in chromosome 12. The cause of the homozygosity of the mutation of the patient is UPD (12) pat.
  
  
  CONCLUSIONS
  To the best of our knowledge, this study is the first UPD (12) pat causing isolated sulfite oxidase deficiency in humans. Even with one parent being a carrier of an autosomal recessive disease, a fetus with the autosomal recessive disease is still possible. This will have clinical impact on genetic counseling.
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China; Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Denise Li-Meng
authors.initials: DL
authors.lastname: Goh
authors.forename: Kin-Chong
authors.initials: KC
authors.lastname: Lau
authors.forename: Hian Tat
authors.initials: HT
authors.lastname: Ong
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency* / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D050862:Oxidoreductases Acting on Sulfur Group Donors; C503599:SUOX protein, human
keywords: Chromosome 12; LOH; SNP array; SUOX; UPD