A novel de novo mutation in LKB1 gene in a Chinese Peutz Jeghers syndrome patient significantly diminished p53 activity

Abstract

Peutz Jeghers syndrome (PJS) is an autosomal dominant disease caused by mutations in the LKB1 gene. We screened for the LKB1 gene mutation in a Chinese PJS patient. Sequence analysis of LKB1 exons showed that there was a novel de novo mis-sense mutation of codon 16 (GAG to GGG) in exon 1 in LKB1 gene in the Chinese PJS patient. Furthermore, we observed that wild type LKB1 expression increased p53 activity, while LKB1 A47G mutation had no such effect on p53 activity, indicating that the mis-sense variant of LKB1 influenced the p53 activation function of LKB1 protein. In addition, real-time RT-PCR analysis revealed that the expression levels of p53 downstream targets were significantly diminished in affected PJS patient compared with those in unaffected parents, further confirming the roles of LKB1 and p53 in PJS pathogenesis. Therefore, a novel PJS associated LKB1 gene mutation is provided, and the roles of LKB1 and p53 in PJS pathogenesis is validated in this research.