中文摘要：

目的对单纯腭裂并全面性癫伴热性惊厥附加症家系进行基因定位,并对候选基因GABRD进行测序研究。方法对家系进行全基因组扫描两点间连锁分析,设计GABRD基因9对外显子-内含子交界处内含子引物,PCR扩增患者及健康对照GABRD基因组序列,测序采用Sanger双脱氧链终止法,PCR产物直接测序,对比分析患者的突变序列及健康对照序列。结果两点连锁分析在1p36区域最大LOD值为1.68。GABRD基因测序显示第4外显子患者的序列分别为T/C和T/T,健康对照的序列分别为T/T和A/C。编码序列分析GGT、GGC及GGA均为甘氨酸。患者GABRD基因mRNA碱基序列为C425T多态性。GABRD第7外显子患者的序列分别为C/T和T/T,健康对照分别为T/T和C/C;异常序列位于mRNA第911碱基处,编码分析AGT及AGC均编码丝氨酸。患者的碱基序列出现了T911C多态性。结论单纯腭裂并全面性癫伴热性惊厥附加症致病基因在1p36区域取得一定的连锁关系,在该家系未发现突变基因;所发现的C425T和T911C单个碱基多态性为其他腭裂及癫家系的连锁分析、关联分析及分子遗传学研究提供了依据。

英文摘要：

Objective Gene mapping of cleft palate only and generalized epilepsy with febrile seizures plus pedigree,and sequencing analysis of the candidate gene GABRD.Methods Genome-wide linkage screen by two-point linkage analysis was used in this pedigree.Primers of intron-exon border were designed for all 9 exons of GABRD,and PCR products from patients and controls were directly sequenced.Mutant sequences from patients were compared to the controls.Results The highest two-point linkage analysis LOD score was 1.68 at 1p36.In GABRD mRNA 425 bp or exon 4,the sequences of patients were T/C and T/T,in normal controls were T/T and A/C,respectively.GGT,GGC and GGA were all coding amino acid Gly.The sequence difference was a C425T single nucleotide polymorphism（SNP）.In mRNA 911 bp or exon 7,the sequences in patients were C/T and T/T,but T/T and C/C in controls.Both AGT and AGC were coding amino acid Ser,it was a T911C SNP.Conclusions A positive linkage result was achieved from this pedigree at 1p36,no obvious mutant sequence was detected from the patients.The GABRD gene C425T and T911C SNP were useful for other gene mapping and gene association analysis in cleft palate and epilepsy pedigrees.