Clinical Analysis Of A Waardenburg Syndrome Type 2 Family And Mutation Detection For MITF Gene

Waardenburg syndrome (WS) is an autosomal-dominant neural crestcell disorder phenotypically characterized by hearing impairment anddisturbance of pigmentation. WS is an autosomal dominant disordercharacterized by sensorineural hearing loss, pigmentary disturbances ofthe skin,hair, and iris, and other developmental defects o It is a clinicallyand genetically heterogeneous disease accounting for more than 2-5% ofthe congenitally deaf population. Not every patient with WS has all of theclinical manifestations of the disease; incomplete forms arecommon.There are four types of this syndrome,such as WSI (MIM19,3500), WSâ…¡(MIM 193510), WSâ…¢(Klein-Waardenburgsyndrome,MIM148820), WSâ…£(Waardenburg-Shah syndrome orWaardenburg-Hirschsprung disease, MIM 277580).Nowadays,greatprogress have been made in the genetic research of WS. The gene MITFis responsible for WSâ…¡.Objiective Comprehensive clinical analysis was made to diagnosea Waardenburg syndrome typeâ…¡family .MITF nine exons were PCRamplified from the genomic DNA of the proband and other familymembers in order to assure the molecular diagnosis.Then to understandWSâ…¡better and explore the molecular genetical mechanism ofWaardenburg syndrome typeâ…¡. Methods This study collected a Chinese family visited in theOutpatient Clinic of Otolaryngology in XiangYa Hospital and 100controls. All participants gave their informed consent prior toparticipation in this study.Clinic evaluation and diagnosis are conductedin the participation.And the proband was primarily defined as WSâ…¡.Withthis foundation,molecular diagnosis was performed. MITF nine exonswere PCR amplified from the genomic DNA of all the family members.Direct DNA sequencing was performed to screen the entire coding regionof the MITF gene for mutations in the MITF.Results The patient was diagnosed as Waardenburg syndrometypeâ…¡.And one heterozygous missense mutation(G650T) in the MITFgene which converts a highly conserved Arg to Ile was found in thesuffer.But the mutation were not found in the normal individuals of thefamily and the 100 controls.Conclusions In this study ,we have identified a novel mutation in theMITF gene in the family with Waardenburg syndrome typeâ…¡. Themolecular findings provide better understanding of the function of MITFgene.As there was no similar patients in patriarchal and matriarchalfamily system ,the proband was a novel mutation individual.Andperhaps his offspring will follow an autosomal dominant inheritance withvariable inter-and infrafamilial expressivity and the incidence is 50%.