Department of Pathology, The University of Hong Kong, Hong Kong, China; Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
Clin Chim Acta. 2013 Nov 15;426:13-7. doi: 10.1016/j.cca.2013.08.013. Epub 2013 Aug 29.
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.
在对一位生化诊断为孤立亚硫酸盐氧化酶缺乏症的先证者进行研究时，我们在该先证者中发现了 SUOX 基因的纯合无义突变。然而，该突变仅在父亲中检测到，而不在母亲中检测到。鉴于母亲非扩增野生型等位基因的等位基因缺失不太可能，因此怀疑存在 SUOX 基因缺失和 12 号染色体父源二体性，该基因位于 12 号染色体上。
为了区分这两种可能的原因，我们使用高密度单核苷酸微阵列在患者及其父母中进行了全基因组微阵列分析。通过 dChip 对患者及其父母的基因组进行了全基因组等位基因共享分析。
在先证者中，全基因组扫描显示整个 12 号染色体的杂合性丢失（LOH）。然而，LOH 是拷贝中性的，因此排除了母亲 SUOX 基因的缺失。在全基因组等位基因共享分析中，先证者与父亲具有高度的等位基因共享，而与母亲仅在 12 号染色体上具有非常低的等位基因共享。患者突变的纯合性原因是 UPD（12）pat。
据我们所知，本研究是首例 UPD（12）pat 导致人类孤立亚硫酸盐氧化酶缺乏症。即使父母一方是常染色体隐性疾病的携带者，胎儿仍有可能患有常染色体隐性疾病。这将对遗传咨询产生临床影响。
