Analysis Of Genetic Characteristics Of A Pedigree With Non-syndromic Hereditary Hearing Loss And Screening Of The Pathogenic Gene

Objective Through the collection the inspection data of medical history information, otology,physical examination and audition test of the family members,we explored the audiological and genetic laws of this pedigree and expecting to find the virulence gene.Methods We carried out the detail investigation into the pedigree and finished the construction of genetic map. At the same time, the data( questionnaire administration,otology,physical examination and audition test) of 14 members were collected while blood samples were collected and stored. Through in-depth analysis of the clinical and genetic phenotype, we predicted the potential genetic models of proband and her patriarchal and maternal members. At the same time, we use the MALD-TOF-MS to detect the samples, so as to carry out a preliminary validation.Results We collected a non-syndrome hereditary hearing loss family with five-generations from Fuqing City, Fujian province due to marriage relationship of two hearing impaired persons.There are 84 members in total, of which 79 were alive and we collected 14 members' blood samples. The paternal family has 40 members alive which not including the proband and 8 deaf subjects. The age of onset ranged from 1 to 55 years. With 8 samples collected(2 with normal hearing and 6 with abnormal hearing),we found that 4 of them showed bilateral extremely severe hearing loss. Through the audiological examination during this study, 2 members were confirmed varying degrees of hearing abnormalities while they hadn't aware of that before. It showed a continuous genetic phenomenon. Deafness occurs in every generation from the thirds. Male and female of each generation can be sick and at least one of the parents of a diseased individual is deaf. In the third generation, the offspring of the female patients might be ill but the males' were health. Screening of 4 common deafness genes in a total of 20 sites, 7 samples were found in the mitochondrial rRNA 1555A>G gene 12 S mutation which were all from the paternal members.The maternal members existing were 39, of whom 14 members were deafness. The age of onset ranged from 6 months to 55 years. There were 6 samples collected from the abnormal and 5 of them showed congenital bilateral severe hearing loss. Three consecutive generations of family members had the incidence of patients putting up a continuous genetic phenomenon. Male and female of each generation can be sick and at least one of the parents of a diseased individual is deaf. If one of someone's parents had a hearing loss while he/she was normal then his/her children had normal hearing function. That tends to be an autosomal dominant mode of inheritance,despite finding no significant mutations in the range of 20 loci.Conclusion A non-syndromic deafness pedigree with two different modes of inheritance was collected through the proband, which established alliances in the deaf and deaf marriage.Paternal family members showed maternal inheritance pattern and members of the matriarchal family performed for non-syndromic autosomal dominant deafness. Using TOF to screen the samples, 20 genes were detected in 4 genes(GJB2?GJB3?SLC26A4 and mt12sRNA).We confirmed the genetic mode of paternal family members was maternal inheritance. As for the maternal members including the proband, several known genes which likely to cause deafness were excluded.