Analyzing The Hereditary Features And The DNA Mutations In A Large Pedigree With Non-sensoneural Hearing Loss

The hereditary hearing loss is congenital or tardy sensoneural hearing impairment induced by the malformation of the inner ear or the dysfunction of the acoustic hair cell of auris interna due to the hereditary factors.Hereditary hearing loss is classified into two types,non-syndromic and syndromic,according to whether accompanied to the other organic deformity.Non-syndromic hearing loss is a hereditary disease with the unique symptom of hearing loss;but syndromic hearing loss exhibits extra symptoms and/or signs apart from hearing loss.The former is responsible for 70%.Hearing loss also can be divided into four catalogs by the mode of inheritance:autosomal dominant inheritance(15%—20%),autosomal recessive inheritance(80%),sex linkage inheritance(1%),and mitochondrial inheritance(1%).About 50 mutational genes had been identified,20 were in autosomal dominant inheritance,19 in autosomal recessive inheritance,7 in sex linkage inheritance and 10 in mitochondrial inheritance.Though it has been got great progress in finding the deafness mutational genes,more mutational genes should be explored.It's helpful to elucidate the mechanism of the deafness in the scale of molecule when finding these genes and understanding the functions of the translated proteins.We collected a large pedigree with feature of deafness in our clinical work.We initially identified the hereditary module conformed to mitochondrial inheritance and we further researched the hereditary feature of this pedigree and drew the map of the pedigree and screened the potential mutational locus.Our research included two parts:1.Investigate the hereditary features;2.Analyze the gene mutations.Part 1.Investigate the hereditary featuresObjective:To screen the hereditary features of the pedigree with hearing impairment.Methods:Collected the detailed clinical history,did the physical examination,performed the PTA,BAEP,MRI&CT examination and established the clinical database.Hearing loss was clinically assessed and the severity of the deafness were classified according to the PTA and the hereditary model assessed initially according to clinical data and pedigree map.Results:This pedigree had the history of aminoglycoside exposure.Besides the hearing impairment,no other abnormalities were found in other systems.Of the family members, 2 exhibited congenital deafness,12 had no hearing deficits,and the remaining 13 suffered mild to profound hearing loss.Conclusion:We identified the hereditary model was non-syndromic mitochondrial inheritance.The deafness grades ranged from normal to profound.Part 2.Analyze the gene mutationsObjective:To screen the mitochondrial DNA(mtDNA) mutations in a large pedigree of aminoglycoside-induced deafness and characterizing the clinical phenotype.Methods:Blood samples were collected from 27 family members(19 matrilineal,8 non-matrilineal) and leukocyte DNA extracted.MtDNA fragments,spanning the 1494 and 1555 location,were amplified by polymerase chain reaction(PCR).PCR products were analyzed by restriction fragment length polymorphism(RFLP) and DNA sequencing.Results:The A1555G mutation was detected in all 19 matrilineal relatives and the C 1494T mutation was not detected.Conclusion:Our results suggested that the A1555G mutation was a hot spot associated with non-syndromic inherited hearing loss that may play a vital role in the pathogenesis of hearing impairment.Additionally,this mutation can result in various grades of deafness.