Contiguous Xp11.4 Gene Deletion Leading to Ornithine Transcarbamylase Deficiency Detected by High-density Single-nucleotide Array

Abstract. Ornithine transcarbamylase (OTC) is one of the enzymes involved in the urea cycle. OTC deficiency, which is caused by impaired synthesis of OTC in the liver, is the most common inherited disease of urea cycle disorders. In this paper, we describe the case of an OTC-deficient Japanese boy wherein an analysis based on high-density single-nucleotide polymorphisms (SNPs) revealed the absence of the entire OTC locus and nearby genes. We identified a deletion on Xp11.4; the size of the deletion fragment was approximately 1 Mb. The deleted region included genes encoding transmembrane 4 superfamily member 2 (TSPAN7), MID1 interacting protein 1 (MID1IP1) and part of the retinitis pigmentosa GTPase regulator (RPGR) in addition to OTC. The results of a high-density SNP assay and PCR confirmed that the mother of the patient was a carrier of the mutation. Previously, determination of breakpoints for large unknown deletions was timeconsuming and laborintensive. However, the use of the widely available DNA chip technology allows for rapid determination of deletion breakpoints; therefore, it will become a standard technique in study of patients with a large genomic deletion of contiguous genes for provision of comprehensive genetic counseling and initiation of clinical management. Key words: OTC deficiency, high-density SNP assay, RPG