Zlotogora J, Furman-Shaharabani Y, Harris A, Barth M L, von Figura K, Gieselmann V
Department of Human Genetics, Hadassah Hospital and Medical School, Hebrew University, Jerusalem, Israel.
J Med Genet. 1994 Sep;31(9):672-4. doi: 10.1136/jmg.31.9.672.
Metachromatic leucodystrophy is an autosomal recessive degenerative disease of the nervous system caused by the deficiency of the lysosomal enzyme arylsulphatase A (ARSA). We report here on the high incidence of late infantile MLD among Muslim Arabs originating from Jerusalem, most probably because of a founder effect. All the patients were found to be homozygous for 459 + 1 G-->A, a mutation which destroys the splice donor site of exon 2 of the ARSA gene. This mutation has been reported to be the most common mutation causing MLD. We studied the ARSA haplotype defined by three intragenic polymorphic sites in DNA samples from Muslim Arab patients from Jerusalem, a Christian Arab patient originating from the region, and eight other white patients, all homozygous for the 459 + 1 G-->A mutation. All the alleles carried the same haplotype which is in complete linkage disequilibrium with the mutation. This finding indicates a common origin for the 459 + 1 G-->A mutation which may have been introduced into Jerusalem at the time of the Crusades.
异染性脑白质营养不良是一种常染色体隐性神经系统退行性疾病，由溶酶体酶芳基硫酸酯酶A（ARSA）缺乏引起。我们在此报告，源自耶路撒冷的穆斯林阿拉伯人患晚期婴儿型MLD的发病率很高，很可能是由于奠基者效应。所有患者均被发现为459 + 1 G→A纯合子，该突变破坏了ARSA基因外显子2的剪接供体位点。据报道，此突变是导致MLD最常见的突变。我们研究了ARSA单倍型，该单倍型由来自耶路撒冷的穆斯林阿拉伯患者、一名来自该地区的阿拉伯基督教患者以及其他八名白人患者（均为459 + 1 G→A突变纯合子）的DNA样本中的三个基因内多态性位点所定义。所有等位基因均携带相同的单倍型，该单倍型与该突变完全连锁不平衡。这一发现表明459 + 1 G→A突变有一个共同起源，可能是在十字军东征时期引入耶路撒冷的。
