Zayed Hatem
Department of Health Sciences, Biomedical Program, Qatar University, Doha, Qatar.
Gene. 2015 Apr 10;560(1):9-14. doi: 10.1016/j.gene.2015.02.009. Epub 2015 Feb 7.
The autosomal recessive Canavan disease (CD) is a neurological disorder that begins in infancy. CD is caused by mutations in the gene encoding the ASPA enzyme. It has been reported with high frequency in patients with Jewish ancestry, and with low frequency in non-Jewish patients. This review will shed light on some updates regarding CD prevalence and causative mutations across the Arab World. CD was reported in several Arab countries such as Saudi Arabia, Egypt, Jordan, Yemen, Kuwait, and Tunisia. The population with the highest risk is in Saudi Arabia due the prevalent consanguineous marriage culture. In several studies, four novel mutations were found among Arabian CD patients, including two missense mutations (p.C152R, p.C152W), a 3346bp deletion leading to the removal of exon 3 of the ASPA gene, and an insertion mutation (698insC). Other previously reported mutations, which led to damage in the ASPA enzyme activities found among CD Arab patients are c.530 T>C (p.I177T), c.79G>A (p.G27R), IVS4+1G>T, and a 92kb deletion, which is 7.16kb upstream from the ASPA start site. This review will help in developing customized molecular diagnostic approaches and promoting CD carrier screening in the Arab world in areas where consanguineous marriage is common particularly within Saudi Arabia.
常染色体隐性遗传性卡纳万病(CD)是一种始于婴儿期的神经疾病。CD由编码天冬氨酸酶(ASPA)的基因突变引起。据报道,该病在犹太裔患者中出现的频率较高,在非犹太裔患者中出现的频率较低。本综述将阐明阿拉伯世界有关CD患病率和致病突变的一些新情况。在沙特阿拉伯、埃及、约旦、也门、科威特和突尼斯等几个阿拉伯国家都有CD病例的报告。由于近亲结婚文化盛行,沙特阿拉伯的人群风险最高。在几项研究中,在阿拉伯CD患者中发现了四种新突变,包括两个错义突变(p.C152R、p.C152W)、一个导致ASPA基因外显子3缺失的3346bp缺失以及一个插入突变(698insC)。在阿拉伯CD患者中发现的其他先前报道的导致ASPA酶活性受损的突变有c.530 T>C(p.I177T)、c.79G>A(p.G27R)、IVS4+1G>T以及一个92kb的缺失,该缺失位于ASPA起始位点上游7.16kb处。本综述将有助于开发定制的分子诊断方法,并在阿拉伯世界近亲结婚普遍的地区,特别是沙特阿拉伯,推动CD携带者筛查。