Microarray analysis unmasked paternal uniparental disomy of chromosome 12 in a patient with isolated sulfite oxidase deficiency

• Published in: Clinica chimica acta 2013-11, Vol.426, p.13-17
• Main Authors: Cho, Sun Young, Goh, Denise Li-Meng, Lau, Kin-Chong, Ong, Hian Tat, Lam, Ching-wan
• Format: Article
• Language: English
• Subjects: Chromosome 12; Chromosomes, Human, Pair 12 - genetics; Female; Humans; Infant; LOH; Loss of Heterozygosity - genetics; Mutation; Oligonucleotide Array Sequence Analysis; Oxidoreductases Acting on Sulfur Group Donors - deficiency; Oxidoreductases Acting on Sulfur Group Donors - genetics; SNP array; SUOX; Uniparental Disomy - genetics; UPD
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.08.013

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. 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. 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. 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. •A genome wide microarray analysis showed paternal uniparental disomy of chromosome 12 in a patient.•To our knowledge, this is the first case of UPD (12) pat identified in an infant.•To our knowledge, this is the first case of sulfite oxidase deficiency associated with UPD.•Single-nucleotide microarray analysis is a useful tool for diagnosing uniparental disomy.