Kandt R S, Pericak-Vance M A, Hung W Y, Gardner R J, Crossen P E, Nellist M D, Speer M C, Roses A D
Division of Neurology in Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Ann N Y Acad Sci. 1991;615:284-97. doi: 10.1111/j.1749-6632.1991.tb37770.x.
Published reports show linkage of tuberous sclerosis (TSC) to either chromosome 9 in some families or chromosome 11 in other families. We studied 243 individuals (82 with TSC) from 16 multigenerational TSC families. The diagnosis of TSC conformed to the criteria of Gomez. Penetrance was estimated at 0.90. DNA markers were analyzed using Southern blotting, probe hybridization, autoradiography, and genetic linkage analysis. Two-point lod scores for TSC were calculated for 43 genetic markers distributed over 11 chromosomes. Tests for homogeneity rejected the null hypothesis of homogeneity. Linkage to TSC was excluded (z less than or equal to -2, theta greater than or equal to 0.05) for 23 of these markers including 9q34 and 11q markers. One family gave z(theta max) = 1.8, theta max = 0.001 with ABO (on 9q34), and two other families attained lod scores greater than 1 for 9q34-region markers. The lod score for TSC versus chromosome 14 marker pAW101 (D14S1) was z(theta max) = 1.98, theta max = 0.15. A single large family has overall negative lod scores for markers localized to both chromosome 9 and chromosome 11. These data confirm genetic heterogeneity in TSC and suggest linkage of some families to 9q34. Furthermore, the data suggest that 14q may be an interesting area.
已发表的报告显示，在一些家族中结节性硬化症（TSC）与9号染色体连锁，而在其他家族中则与11号染色体连锁。我们研究了来自16个多代TSC家族的243名个体（82名患有TSC）。TSC的诊断符合戈麦斯标准。外显率估计为0.90。使用Southern印迹法、探针杂交、放射自显影和基因连锁分析对DNA标记进行分析。计算了分布在11条染色体上的43个遗传标记的TSC两点连锁值。齐性检验拒绝了齐性的零假设。包括9q34和11q标记在内的23个这些标记与TSC的连锁被排除（z小于或等于 -2，θ大于或等于0.05）。一个家族与ABO（位于9q34）的z(θmax)=1.8，θmax = 0.001，另外两个家族对于9q34区域的标记获得的连锁值大于1。TSC与14号染色体标记pAW101（D14S1）的连锁值为z(θmax)=1.98，θmax = 0.15。一个大家族对于定位于9号染色体和11号染色体上的标记总体连锁值为阴性。这些数据证实了TSC的遗传异质性，并提示一些家族与9q34连锁。此外，数据表明14q可能是一个有趣的区域。
