Auger K J, Ajene A, Lerner T
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Mol Genet Metab. 1999 Apr;66(4):332-6. doi: 10.1006/mgme.1999.2805.
Marked clinical heterogeneity is seen in the late-infantile subtype of NCL (LINCL), complicating genetic analysis. In addition to the classical subtype, encoded by CLN2 on chromosome 11p15.5, several variant subtypes have also been described. In this paper, we report our progress in cloning a variant LINCL gene mapped in a small group of Costa Rican families. Clinically, these patients appear similar to classical LINCL patients, except onset of the disease is delayed and the course is milder. Extended haplotype analysis confirms the localization of this gene to chromosome 15q21-22, where CLN6 has also been mapped. Using now-standard positional cloning techniques, we have developed a physical map of our candidate region. These clones have been used to order genetic markers, STSs, and ESTs in this region and will be used for the identification of the disease gene transcript.
在神经元蜡样脂褐质沉积症（NCL）的晚婴儿型（LINCL）中可见明显的临床异质性，这使基因分析变得复杂。除了由11号染色体p15.5上的CLN2编码的经典亚型外，还描述了几种变异亚型。在本文中，我们报告了在克隆一个定位在一小群哥斯达黎加家族中的变异LINCL基因方面取得的进展。临床上，这些患者与经典LINCL患者相似，只是疾病的发病延迟且病程较轻。扩展单倍型分析证实该基因定位于15号染色体q21 - 22，CLN6也定位于此。使用目前标准的定位克隆技术，我们构建了候选区域的物理图谱。这些克隆已用于在该区域排列遗传标记、序列标签位点（STS）和表达序列标签（EST），并将用于鉴定疾病基因转录本。
