A Study On Genotyping In Large Neonatal Samples Of Deafness And Related Factors In Eastern And Western Regions Of Hubei Province

Hearing loss is the most common sensory dysfunction in humans.360 million people worldwide suffer from hearing loss,and three newborns out of every thousand are born with hearing loss or acquire it soon after birth.Universal screening of newborn hearing,which greatly reduces the time to discovery of neonatal deafness,has been shown to allow effective early intervention.There is still much room for improvements to neonatal deafness screening procedures,and genetic screening may be an effective accompaniment to traditional hearing screening.More than 50% of deafness is caused by genetic factors.Genetic screening can help identify the etiology of congenital deafness,identify those at risk of late onset deafness,and prevent deafness due to exposure to some medications.Previous studies have found that GJB2,SLC26A4,GJB3 and other genes are closely related to hereditary deafness,but most of them have a low incidence in the Chinese population,lacking the value of large-scale screening.The demographic characteristics of the eastern and western regions of Hubei Province are unique due to the gathering of ethnic minority residents and the relative economic lag.Neonatal genetic screening can reveal the local frequency distribution and genetic differences of deafness gene mutations.This study first selected four genetic variants,GJB2 c.235 delC,SLC26A4 c.919-2A>G,MTRNR1 m.1555A>G and m.1494C>T,which are among the most common in Chinese deaf-mute people.191104 newborns born from 2017 to 2018 in the eastern and western regions of Hubei Province were genetically screened by real time PCR and the genotypes were identified.8411 neonates who received both hearing and genetic screens in 2017 were followed up to collect additional data,and the correlation of genetic and environmental factors with hearing screening results were analyzed.This study found that a total of 3.26%(6235/191104)of newborns carried at least one deafness gene mutation.Among them,the GJB2 c.235 delC carrier rate was 2.15%(4115/191104),and 33 cases were homozygous deletions;the SLC26A4 c.919-2A>G carrier rate was 0.89%(1700/191104),and two cases were homozygous mutations;497 newborns carried the mitochondrial MTRNR1 mutations,457 of which were m.1555A>G(carrier rate of 0.24%).Only 0.021%(40/191104)of the newborns carried the m.1494C>T mutation.Comparing the participants from the east and the west of the province found that the frequencies of MTRNR1 gene variants showed significant difference.The frequency of GJB2 c.235 delC and MTRNR1 mutations among newborns in Huangshi City were higher than in other cities,the SLC26A4 c.919-2A>G mutations in Xiaogan and Yichang were significantly relatively high,while the mutation rate of MTRNR1 in Huanggang City was lower than that in other cities.The carrier rate within each ethnic group also showed differences.The carrier rate of MTRNR1 m.1555A>G among the Tujia people was significantly higher than in the Han population.The follow-up study found that the identification of hearing loss via the hearing screening of newborns carrying GJB2 and SLC26A4 mutations was significantly higher than among newborns with the common alleles,it confirms that these two genes are exact deafness-related genes.The mutation of MTRNR1 was not significantly different with the common alleles,which proved that most patients with aminoglycoside-induced deafness did not show hearing loss when they were not exposed to this drug.A family history of congenital hearing loss,complications at birth,and being born in winter were also found to be associated with a significantly increased risk of hearing loss.Additionally,Miao neonates also exhibited a higher risk of hearing loss than other populations.The mother's pregnancy history was not seen to be a risk factor for hearing loss.Neonatal deafness genetic screening is a project with important social and economic benefits,which is of great help to early detection of deafness risk groups.The study established a large-scale deafness genetic screening platform in Hubei Province,and not only found the differences of frequencies of variants in different regions and nationalities,determined the mode and value of genetic screening for deafness,provided theoretical basis and data support for genetic counseling,early diagnosis,intervention and treatment of high-risk population for deafness,guide the MTRNR1 gene mutation population and maternal relatives safe medication;but also verified the commonness and complementarity of the two screening methods,which could be used to improve the screening model for newborns with deafness.