TMPRSS۳, a critical gene for cochlear hair cell survival and its role in hearing loss: a literature review

Background and objectiveHearing loss (HL), one of the most common sensory impairments, is the fourth andsecond disability in the world and Iran, respectively. The prevalence of HL in Iran is ۱in ۱۶۶ infants, which is estimated to be ۲ to ۳ times higher than in other parts of theworld. Hearing loss is classified based on cause, type, age of onset, and syndromic/non-syndromic. Non-syndromic genetic deafness is highly heterogeneous in terms ofclinical manifestations, the pattern of inheritance, and genetic causes. TMPRSS۳ is amember of the type II membrane serine protease family, in which mutations causechildhood (DFNB۸) or congenital onset (DFNB۱۰) of autosomal recessive nonsyndromichearing loss (ARNSHL). TMPRSS۳ is expressed in the organ of Corti, thestria vascularis and in the spiral ganglion, and activates the epithelial sodium channel,thus affecting cochlear sodium concentrations.Search MethodAn overview of the organized literature was conducted in the Google Scholardatabase. Out of ۱۷۹۰ articles from ۲۰۰۰ to ۲۰۲۲, related articles were screened andstudied.FindingsIn overall, GJB۲ is the most common mutated gene in ARNSHL. However, ARNSHLis genetically highly heterogeneous in which, in addition to GJB۲, many other genesare involved. Unlike GJB۲, TMPRSS۳ is the least common in Iran, while in patientsfrom Pakistani, Tunisia, Korea, and Turkey it accounts for about ۱.۸%, ۵%, ۵.۹%, and۱۲%, respectively. As far as being studied, only one homozygous duplication mutationin exon ۴ of the TMPRSS۳ gene has been reported in Iranian population. BecauseTMPRSS۳ is localized in the endoplasmic reticulum membranes, undergoes cleavesand activates a selective sodium channel called ENaC, while theTMPRSS۳ mutantproteins, which cause deafness, are all unprocessed and inactive. It should be notedthat ENaC is expressed in many tissues of sodium reabsorption and is a good candidate for sodium reabsorption from endolymph, which plays an important role indeafness.ConclusionGiven the prevalence of consanguineous marriages in Iran, this population is avaluable resource for studying heterogeneous genetic diseases such as hearing loss.Genetic counseling and testing for families with HL can be effective inpreimplantation genetic diagnosis, newborn screening, and preventing the recurrenceof the condition in affected families.

کلیدواژه ها:

Hearing impairment ، Non-syndromic ، TMPRSS۳ ، Iran