Rafi M A, Luzi P, Zlotogora J, Wenger D A
Department of Medicine (Medical Genetics), Jefferson Medical College, Philadelphia, PA 19107, USA.
Hum Genet. 1996 Mar;97(3):304-8. doi: 10.1007/BF02185759.
Infantile Krabbe disease is a severe, fatal autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity. It is relatively common in two separate inbred communities in Israel. In the Druze community in Northern Israel and two Moslem Arab villages located near Jerusalem the incidence of Krabbe disease is about 1 in 100-150 live births. With our cloning of the GALC gene, mutation analysis of these populations was undertaken. The Moslem Arabs were homozygous for two mutations in the GALC gene; a T-to-C transition at CDNA position 1637 (counting from the A of the initiation codon), which is considered a polymorphism and a G-to-A transition at position 1582, which changes the codon for aspartic acid to one for asparagine. The Druze patients are homozygous for a T-to-G transversion at position 1748, which changes the codon for isoleucine to one for serine. Expression studies confirmed the deleterious nature of these mutations. The development of a simple polymerase chain reaction (PCR) amplification and restriction enzyme digestion method to identify these alleles will lead to accurate carrier testing and improved genetic counseling for interested individuals in these communities.
婴儿型克拉伯病是一种严重的、致命的常染色体隐性疾病，由半乳糖脑苷脂酶（GALC）活性缺乏引起。它在以色列两个不同的近亲群体中相对常见。在以色列北部的德鲁兹社区以及位于耶路撒冷附近的两个穆斯林阿拉伯村庄，克拉伯病的发病率约为每100 - 150例活产中有1例。随着我们克隆出GALC基因，对这些人群进行了突变分析。穆斯林阿拉伯人在GALC基因中有两个突变的纯合子；cDNA位置1637（从起始密码子的A开始计数）处的T到C转换，这被认为是一种多态性，以及位置1582处的G到A转换，该转换将天冬氨酸密码子变为天冬酰胺密码子。德鲁兹患者在位置1748处为T到G的颠换纯合子，该转换将异亮氨酸密码子变为丝氨酸密码子。表达研究证实了这些突变的有害性质。开发一种简单的聚合酶链反应（PCR）扩增和限制性内切酶消化方法来鉴定这些等位基因，将为这些社区中有兴趣的个体带来准确的携带者检测和更好的遗传咨询。
