Abstract:

Objective · To analyze the genetic characteristics of Muckle-Wells syndrome in a Chinese family based on a case misdiagnosed as nonsyndromic deafness. Methods · The medical history, family history, physical, and audiological examinations were performed for a deaf patient. The familial pedigree was drawn and genetic characteristics were analyzed. Screening for exons and flanking intron sequences in 138 genes known to be associated with deafness was performed for the proband with deafness-targeted next generation sequencing. The whole exon sequencing was conducted for 3 affected and 1 unaffected familial members. The genotype-phenotype co-segregation was verified with Sanger sequencing for Candidate mutations. Results · The deafness family contained 11 members with 3 generations. Inquiries revealed that 9 of them were deaf with bilateral, late onset, and progressive hearing loss, which was consistent with autosomal dominant inheritance. One hundred and thirty-eight genes known to be associated with deafness were ruled out with deafness-targeted next generation sequencing. The whole exon sequencing revealed an E313K mutation in NLRP3 and the co-segregation between E313K and the deafness phenotype in this family was confirmed by Sanger sequencing. Conclusion · A Chinese family with an autosomal dominant hereditary hearing loss was diagnosed as Muckle-Wells syndrome for the first time. E313K mutation in the NLRP3 gene was identified as the causative gene mutation.

Key words: Muckle-Well Syndrome, exome sequencing, deafness, autosomal dominant hereditary