Mitchison H M, O'Rawe A M, Lerner T J, Taschner P E, Schlumpf K, D'Arigo K, de Vos N, Gormally E, Phillips H A, Thompson A D
Department of Paediatrics, University College London Medical School, Rayne Institute, United Kingdom.
Am J Med Genet. 1995 Jun 5;57(2):312-5. doi: 10.1002/ajmg.1320570241.
Haplotype analysis in a collaborative collection of 143 families with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielmeyer-Vogt-Sjögren) disease has permitted refined localization of the disease gene, CLN3, which was assigned to chromosome 16 in 1989. Recombination events in four maternal meioses delimit new flanking genetic markers for CLN3 which localize the gene to the chromosome interval 16p12.1-11.2 between microsatellite markers D16S288 and D16S383. This narrows the position of CLN3 to a region of 2.1 cM, a significant reduction from the previous best interval. Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers within the D16S288-D16S383 interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298. Analysis of markers across the D16S288-D16S383 region in four families with a variant form of JNCL characterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of chromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL.
对143个患有青少年型神经元蜡样脂褐质沉积症（JNCL）或巴滕病（施皮尔曼 - 沃格特 - 舍格伦病）的家庭组成的合作样本进行单倍型分析，有助于对疾病基因CLN3进行精细定位，该基因于1989年被定位到16号染色体上。四个母本减数分裂中的重组事件确定了CLN3新的侧翼遗传标记，将该基因定位到微卫星标记D16S288和D16S383之间的16p12.1 - 11.2染色体区间。这将CLN3的位置缩小到2.1厘摩的区域，与之前的最佳区间相比有显著缩小。利用单倍型，对D16S288 - D16S383区间内遗传标记与CLN3之间存在的强连锁不平衡进行分析，结果表明CLN3与基因座D16S299和D16S298距离最近。对四个组织学特征为胞体颗粒嗜锇沉积（GROD）的JNCL变异型家庭中D16S288 - D16S383区域的标记进行分析，排除了该基因座与16号染色体CLN3区域的连锁关系，提示具有GROD的JNCL不是JNCL的等位基因形式。
