Abstract：
BACKGROUND: AICA (5-aminoimidazole-4-carboxamide) ribosiduria is an inborn error in purine biosynthesis caused due to biallelic pathogenic variants in the 5-aminoimidazole-4-carboxamide ribonucleotide-formyltransferase/imp cyclohydrolase (ATIC) gene located on chromosome 2q35. ATIC codes for a bifunctional enzyme, AICAR transformylase and inosine monophosphate (IMP) cyclohydrolase, which catalyse the last two steps of de novo purine synthesis. This disorder has been previously reported in only 4 cases worldwide, and herein, we report the first from India.
METHODS: The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant.
CONCLUSIONS: This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling.
METHODS: The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant.
CONCLUSIONS: This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling.
摘要：
背景：AICA（5-氨基咪唑-4-甲酰胺）ribosiduria是嘌呤生物合成中的先天性错误，是由于位于染色体2q35上的5-氨基咪唑-4-甲酰胺核糖核苷酸-甲酰转移酶/imp环水解酶（ATIC）基因的双等位基因致病变体引起的。ATIC编码了一种双功能酶,AICAR转化酶和肌苷一磷酸（IMP）环水解酶，催化嘌呤从头合成的最后两步。这种疾病以前在全球仅有4例报道，在这里，我们报道第一个来自印度。
方法：呈现全球发育迟缓的先证者，发育性髋关节发育不良（DDH），无花性心脏病和眼球震颤样眼球运动。全外显子组测序(WES)鉴定了ATIC中的复合杂合致病变体。一种新的剪接位点变体；c.1321-2A>G和先前报道的错义变体；c.127A>G（p。Lys426Arg）被鉴定。父母的分离分析表明，父亲是剪接位点变异的杂合携带者，母亲，错义变体的杂合载体。
结论：这种罕见的ATIC缺乏症嘌呤生物合成遗传疾病是印度报道的首例病例。早期诊断导致早期介入治疗和遗传咨询。
方法：呈现全球发育迟缓的先证者，发育性髋关节发育不良（DDH），无花性心脏病和眼球震颤样眼球运动。全外显子组测序(WES)鉴定了ATIC中的复合杂合致病变体。一种新的剪接位点变体；c.1321-2A>G和先前报道的错义变体；c.127A>G（p。Lys426Arg）被鉴定。父母的分离分析表明，父亲是剪接位点变异的杂合携带者，母亲，错义变体的杂合载体。
结论：这种罕见的ATIC缺乏症嘌呤生物合成遗传疾病是印度报道的首例病例。早期诊断导致早期介入治疗和遗传咨询。
