ABSTRACT
BACKGROUND: Research on mapping the gene for benign familial infantile convulsion(BFIC) has been conducted mainly in western countries. Although three chromosome loci have been found by three research groups, up to now the gene responsible for BFIC has been neither found nor identified. Mapping the gene and studying locus heterogeneity is the first step toward cloning the disease gene.OBJECTIVE: To explore the relation between BFIC loci and the gene for BFIC in five Chinese pedigrees with BFIC. Locus heterogeneity among these pedigrees will be revealed based on the findings so as to further map the gene.DESIGN: Retrospective and observational controlled study using five Chinese pedigrees with BFIC as subjects.SETTING: Laboratory of cell biology and medical genetics in a university.PARTICIPANTS: The study was conducted in the Laboratory of Cell Biology and Medical Genetics of Zhengzhou University from July 2001 to July 2003. Five BFIC pedigrees of 70 subjects, 28 BFIC patients and 42 non-BFIC patients, from Xinxiang, Nanyang, Zhoukou, and Hebi of Henan Province,China, were involved. Inclusion criteria: Those met the epileptic seizure classification criteria issued by the International Anti-epilepsy Commissi6n[2].Exclusion criteria: The patients were excluded from the group of the affected members if any of the three examinations, namely, interictal electroencephalograms, computed-tomography scanning and magnetic-resonance imagining, was abnormal. The same exclusion criteria applied to patients who had suffered either toxicosis or cerebral damage.METHODS: To get the genotypes of these family members, such techniques as polymerase chain reaction, polyacrlamide and agarose gels electrophresis and sliver straining were used. The procedure was as follows: first, DNA was extracted from the peripheral blood of the members of five pedigrees with BFIC. Then, six short tandem repeat(STR) loci, namely, D19S245,D19S250, D16S3131, D16S3133, D2S399 and D2S2330, were used to detect genotype of each family member, followed by input of the genotypes into the computer and linkage analysis by MLINK program from LINKAGE package. Finally, the results of linkage analysis were analyzed by HOMOGM program and locus heterogeneity was obtained.MAIN OUTCOME MEASURES: Analysis results of genotype of each subject and the results of heterogeneity detection.RESULTS: One maximum two-point limit of detection (LOD) score of 2. 151 for D19S250 was obtained at recombination rate of 0. 000 under autosomal dominant model with 90% penetrance. For D16S3131, two maximum two-point LOD scores of 1. 056 and 1. 155 were obtained at recombination rate of 0. 085 under autosomal dominant model with 70% and 60% penetrance. This suggested that the gene for BFIC pedigree might be linked to D16S3131 or D19S250. At the other DNA markers, no information suggested that linkage was produced. The results of heterogeneity detection showed that there was locus heterogeneity among the BFIC pedigrees.CONCLUSION: The gene for BFIC may be linked to D16S3131 or D19S250. Heterogeneity exists in BFIC, which serves as primary information for the further study of mapping the disease gene for BFIC.