Shaag A, Anikster Y, Christensen E, Glustein J Z, Fois A, Michelakakis H, Nigro F, Pronicka E, Ribes A, Zabot M T
Metabolic Unit, Shaare-Zedek Medical Center, Jerusalem, Israel.
Am J Hum Genet. 1995 Sep;57(3):572-80.
Canavan disease is an infantile neurodegenerative disease that is due to aspartoacylase deficiency. The disease has been reported mainly in Ashkenazi Jews but also occurs in other ethnic groups. Determination of enzymatic activity for carrier detection and prenatal diagnosis is considered unreliable. In the present study, nine mutations were found in the aspartoacylase gene of 19 non-Jewish patients. These included four point mutations (A305E [39.5% of the mutated alleles], C218X [15.8%], F295S [2.6%], and G274R [5.3%]); four deletion mutations (827delGT [5.3%], 870del4 [2.6%], 566del7 [2.6%], and 527del6 [2.6%]); and one exon skip (527del108 [5.3%]). The A305E mutation is pan-European and probably the most ancient mutation, identified in patients of Greek, Polish, Danish, French, Spanish, Italian, and British origin. In contrast, the G274R and 527del108 mutations were found only in patients of Turkish origin, and the C218X mutation was identified only in patients of Gypsy origin. Homozygosity for the A305E mutation was identified in patients with both the severe and the mild forms of Canavan disease. Mutations were identified in 31 of the 38 alleles, resulting in an overall detection rate of 81.6%. All nine mutations identified in non-Jewish patients reside in exons 4-6 of the aspartoacylase gene. The results would enable accurate genetic counseling in the families of 13 (68.4%) of 19 patients, in whom two mutations were identified in the aspartoacylase cDNA.
卡纳万病是一种由于天冬氨酸酰基转移酶缺乏引起的婴儿期神经退行性疾病。该疾病主要在德系犹太人中报道，但也发生在其他种族群体中。用于携带者检测和产前诊断的酶活性测定被认为不可靠。在本研究中，在19名非犹太患者的天冬氨酸酰基转移酶基因中发现了9种突变。其中包括4种点突变（A305E[占突变等位基因的39.5%]、C218X[15.8%]、F295S[2.6%]和G274R[5.3%]）；4种缺失突变（827delGT[5.3%]、870del4[2.6%]、566del7[2.6%]和527del6[2.6%]）；以及1种外显子跳跃（527del108[5.3%]）。A305E突变在欧洲广泛存在，可能是最古老的突变，在希腊、波兰、丹麦、法国、西班牙、意大利和英国血统的患者中均有发现。相比之下，G274R和527del108突变仅在土耳其血统的患者中发现，而C218X突变仅在吉普赛血统的患者中发现。在卡纳万病的重度和轻度形式患者中均发现了A305E突变的纯合性。在38个等位基因中的31个中发现了突变，总体检测率为81.6%。在非犹太患者中鉴定出的所有9种突变都位于天冬氨酸酰基转移酶基因的第4至6外显子中。这些结果将使19名患者中的13名（68.4%）的家庭能够获得准确的遗传咨询，在这些患者的天冬氨酸酰基转移酶cDNA中鉴定出了两种突变。
