关键词: TSC1基因, 结节性硬化症, 遗传学

Abstract: Objective To summarize and analyze the clinical phenotype and genetic characteristics of a family with TSC1 gene mutation in tuberous sclerosis,so as to provide evidence for genetic counseling.Methods The clinical phenotypes of 6 probands and their grandmothers,aunts,aunts,mothers and sisters in the three generations of close relatives of the family were consistent with tuberous sclerosis.The probands and their parents and sisters were amplified by PCR for all coding regions and flanking shear sites of TSC1 and TSC2 genes,and the products were sequenced for mutation analysis.At the same time,35 unrelated normal controls were detected,The correlation between the gene variation and clinical phenotype was further analyzed.Results NM was found in exon 10 of TSC1 gene in proband,mother and sister_ 000368.5:c.917_ The 923upGTGCTAC mutation resulted in abnormal protein level(the amino acid at the position of p.Ser309Cysfs * 34309 changed from serine to cysteine,and from the position of 309,continued translation 34 met the termination codon,resulting in early termination of protein translation).The father did not find the mutation,and the father's clinical phenotype was normal,and the mutation was not detected in 35 normal controls.After searching HGMD database,this mutation is a new mutation,and there has been no report of this mutation in the past,which is consistent with the genetic co-segregation of disease phenotypes in the family.Conclusion TSC1 gene c.917_ The 923 base repeat frameshift mutation may be the cause of tuberous sclerosis in this family.The clinical phenotype of TSC1 gene mutation at the same site in the same family has strong heterogeneity.

Key words: TSC1 gene, Tuberous sclerosis, Genetics