[Genetic analysis of novel MKKS variants in a Chinese patient with Bardet-Biedl syndrome].

OBJECTIVE

To explore the genetic basis of a Chinese patient with Bardet-Biedl syndrome (BBS).

METHODS

Clinical data of the patient was analyzed. Next-generation sequencing was carry out to screen pathogenic variants, and candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics.

RESULTS

Next-generation sequencing revealed that the proband has harbored two pathogenic variants of the MKKS gene (c.635C>T and c.1664C>G) and one likely pathogenic variant of the TMEM67 gene (c.2498T>C). Sanger sequencing of the proband and her mother confirmed that the proband has harbored two compound heterozygous MKKS variants and a heterozygous TMEM67 variant. Both of the MKKS variants were previously unreported and located in a highly conserved domain and predicted to be disease-causing by bioinformatic analysis.

CONCLUSION

The two novel MKKS/BBS6 variants probably underlay the BBS in the proband. The TMEM67 variant may have an epistatic effect on mutations of BBS-associated loci.