Diagnosis of two cases from one family with Joubert syndrome caused by novel mutations of TCTN1 gene by whole exome sequencing

Objective To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). Methods Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. Results Two novel TCTN1 mutations, c. 342-8A>G and c. 1494+ 1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. Conclusion The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS. Key words: Joubert syndrome; TCTN1gene; Whole exome sequencing; Novel mutation