Ornithine transcarbamylase gene mutations and genotype-phenotype correlation in Polish patients with hyperammonemia type 2
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Ornithine (OTC) deficiency is an X-linked disorder of the urea cycle inherited by a partially dominant trait. We studied one boy with a positive family history of sudden infant death syndrome (SIDS) and four girls with suspected OTC deficiency basing on pedigree analysis, spontaneous episodes of hyperammonemia and orotic aciduria, and on results of the allopurinol loading test. Four different point mutations, N198K in exon 6, A209V and E326K in exon 9, and IVS nt-2 aRg in splice acceptor site in intron 7 were identified in the OTC gene. In addition, one common polymorphism in exon 8 (Q270R) with normal OTC activity was observed. All the mutations were detected in heterozygous girls and, except one, in the patients' asymptomatic mothers. In the latter single case the mutation had occurred de novo. All of the affected patients developed a positive allopurinol test. Four affected but asymptomatic women (mothers and a sister of the patients) revealed normal or only slightly increased orotic aciduria following allopurinol ingestion. Our observation supports the probability of undefined or false negative allopurinol test results reported previously for heterozygous females.
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E. Popowska, The Children's Memorial Health Institute, Department of Medical Genetics, Al. Dzieci Polskich 20, 04-736 Warszawa, Poland