Mitchison H M, O'Rawe A M, Taschner P E, Sandkuijl L A, Santavuori P, de Vos N, Breuning M H, Mole S E, Gardiner R M, Järvelä I E
Department of Paediatrics, University College London Medical School, United Kingdom.
Am J Hum Genet. 1995 Mar;56(3):654-62.
The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjögren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers--D16S288, D16S299, D16S298, and SPN--are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These markers span a candidate region of approximately 2.1 cM. CLN3 is most prevalent in northern European populations and is especially enriched in the isolated Finnish population, with an incidence of 1:21,000. Linkage disequilibrium mapping was applied to further refine the localization of CLN3 in 27 Finnish families by using linkage disequilibrium data and information about the population history of Finland to estimate the distance of the closest markers from CLN3. CLN3 is predicted to lie 8.8 kb (range 6.3-13.8 kb) from D16S298 and 165.4 kb (132.4-218.1 kb) from D16S299. Enrichment of allele "6" at D16S298 (on 96% of Finnish and 92% of European CLN3 chromosomes) provides strong evidence that the same major mutation is responsible for Batten disease in Finland as in most other European countries and that it is therefore not a Finnish mutation. Genealogical studies show that Batten disease is widespread throughout the densely populated regions of Finland. The ancestors of two Finnish patients carrying rare alleles "3" and "5" at D16S298 in heterozygous form originate from the southwestern coast of Finland, and these probably represent other foreign mutations. Analysis of the number and distribution of CLN3 haplotypes from 12 European countries provides evidence that more than one mutation has arisen in Europe.
巴顿病（青少年型神经元蜡样脂褐质沉积症，即施皮勒梅耶 - 舍格伦病）的致病基因CLN3定位于16p11.2 - 12.1。在来自16个不同国家的142个家庭中，四个微卫星标记——D16S288、D16S299、D16S298和SPN——与CLN3处于强连锁不平衡状态。这些标记跨越了一个约2.1厘摩的候选区域。CLN3在北欧人群中最为常见，在芬兰孤立人群中尤为富集，发病率为1:21,000。通过使用连锁不平衡数据以及芬兰人口历史信息来估计最接近标记与CLN3的距离，应用连锁不平衡图谱法在27个芬兰家庭中进一步精确定位CLN3。预计CLN3距离D16S298为8.8千碱基对（范围6.3 - 13.8千碱基对），距离D16S299为165.4千碱基对（132.4 - 218.1千碱基对）。D16S298上“6”等位基因的富集（芬兰CLN3染色体的96%以及欧洲CLN3染色体的92%）有力地证明，芬兰和大多数其他欧洲国家的巴顿病是由相同的主要突变引起的，因此这不是芬兰特有的突变。系谱研究表明，巴顿病在芬兰人口密集地区广泛存在。两名芬兰患者以杂合形式在D16S298携带罕见等位基因“3”和“5”，他们的祖先来自芬兰西南海岸，这些可能代表其他外来突变。对来自12个欧洲国家的CLN3单倍型数量和分布的分析表明，欧洲出现了不止一种突变。
