良性家族性婴儿惊厥一家系遗传连锁分析和基因定位研究

Linkage analysis and gene mapping of one Chinese family with benign familial infantile convulsions

摘要:

目的：对1个良性家族性婴儿惊厥(benign familial infantile convulsions, BFIC)家系进行遗传连锁分析和基因定位，以探讨BFIC的分子发病机制。方法：调查一个4代BFIC家系。选择位于染色体19q12~q13.1的D19S245和D19S250，16p12~q12的D16S3131和D16S3133，2q24的D2S156和D2S286，20q13.3的D20S480和D20S481共8个短串连重复序列（short tandem repeat，STR）作为遗传标记，应用聚合酶链反应(PCR)，变性聚丙烯酰胺凝胶电泳(PAGE) 和银染技术，采用LINKAGE软件包中的MLINK程序计算LOD值，根据LOD值判断连锁关系。结果：当重组率在0.000至0.01之间，在染色体19q12~13.1、16p12~q12及2q24区域的遗传标记LOD值均小于-2.0；在20q13.3(D20S481)区域，当重组率为0.000时，LOD值为0.3，当重组率为0.01时，LOD值为0.25。结论：排除该家系与染色体19q12~13.1、16p12~q12及2q24区域的遗传标记存在连锁关系的可能；在20q13.3区域，虽然没有显著性意义，但不能排除与20q13.3区域连锁的可能。［中国当代儿科杂志，2010，12（2）：89-92］

Abstract:

OBJECTIVE: The present study performed linkage analysis and gene mapping to find the possible chromosome locus harboring in one family with benign familial infantile convulsions (BFIC) and investigate the possible molecular pathogenesis of BFIC. METHODS: A four-generation family with BFIC was investigated. The family was genotyped using eight hypervariable microsatellite markers covering four loci: D19S245 and D19S250 for the 19q12-13.1 region, D16S3131 and D16S3133 for the 16p12-q12 region, D2S156 and D2S286 for the 2q24 region, and D20S480 and D20S481 for the 20q13.3 region. Polymorphism fragments were amplified using polymerase chain reaction (PCR) method. PCR products for the markers were subjected to electrophoresis on 8% denatured polyacrylamide gel and silver staining for length judgment of amplification fragment. Linkage analysis was performed by use of MLINK in the LINKAGE computer package. Two-point LOD scores were calculated to estimate the linkage relationship. RESULTS: The two-point LOD scores were less than -2.0 for the genetic markers at chromosomes 19q12-13.1, 16p12-q12 and 2q24 at the recombination rate between 0.000 and 0.01. The two-point LOD scores for D20S481 at the 20q13.3 region were 0.3 and 0.25 at the recombination rate of 0.000 and 0.01, respectively. CONCLUSIONS: There is no evidence that this family with BFIC is linked to one of the following loci: 19q12-13.1, 16p12-q12 and 2q24, but a possible linkage with 20q13.3 region cannot be excluded.［Chin J Contemp Pediatr, 2010, 12 (2):89-92］