DFNB1 locus has been linked to a nonsyndromic “invisible disability” called congenital sensorineural hearing loss and deafness. Mutations of GJB2 and GJB6 genes are associated with deafness at the DFNB1 locus. The d...DFNB1 locus has been linked to a nonsyndromic “invisible disability” called congenital sensorineural hearing loss and deafness. Mutations of GJB2 and GJB6 genes are associated with deafness at the DFNB1 locus. The diagnosis of DFNB1 is made with molecular genetic testing. DNA-based testing can be used both prenatally and postnatally. Purpose: to get evidence for implementation of newborn hearing screening programs at national level;to use the molecular testing of children at risk for confirmation of diagnosis and early intervention. OAEs and ABR were performed for 4303 newborns. Audiologic evaluation of 38 children suspected of having hearing loss was performed too. Physical examinations and family history were used to get information about congenital deafness. DNA from blood samples was isolated, and two PCR multiplex assays were developed to detect DFNB1 mutations. Only 23 newborns were screened positive. Newborns were referred to audiologic evaluation, genetic counseling and testing for the etiologic diagnosis. Physical examination revealed no other abnormal findings. GJB2 mutations were detected in 36.03% of patients, and all of them have 35delG mutation. None of them was found to have GJB6 mutations. Our results suggested that molecular testing was an accurate method of early determining cause of congenital hearing loss and helped us to exclude GJB6 gene from the routine hearing screening protocol.展开更多
Background The DFNB1 locus, which contains the gap junction beta-2 （GJB2） and gap junction beta-6 （GJB6） genes, plays a key role in the nonsyndromic and sporadic hearing impairment. Mutations of DFNB1 result in au...Background The DFNB1 locus, which contains the gap junction beta-2 （GJB2） and gap junction beta-6 （GJB6） genes, plays a key role in the nonsyndromic and sporadic hearing impairment. Mutations of DFNB1 result in autosomaJ recessive nonsyndromic hearing impairment （ARNSHI）. Previous researches have identified mutations in GJB2 and GJB6, but single nucleotide polymorphisms （SNPs） of DFNB1 locus have not been studied. So we chose five SNPs to evaluate whether there is difference between deafness people and normal-hearing people in Han Chinese. Methods Five SNPs in the DFNB1 region were examined using a case-control association study between cases with sporadic hearing impairment and controls with normal hearing. The HWEsoft and SHEsis softwares were used to analyze the results. Results Single-locus association analysis showed a positive association for three SNPs： rs9315400, rs2274084 and 235delC. When we compared the distributions of the haplotypes, we also found significant differences between cases and controls in the haplotype combination of rs2274084 and rs2274083 （Х^2=12.978, df=3, global P=0.004719）. Conclusions The haplotypes composed of rs2274084 and rs2274083 suggested that C-C may be a risk haplotype for the sporadic hearing impairment while T-T may be protective against hearing impairment. From that point of view, we can conclude that the SNPs of DFNB1 locus also plays an important role in sporadic hearing impairment cases.展开更多
文摘DFNB1 locus has been linked to a nonsyndromic “invisible disability” called congenital sensorineural hearing loss and deafness. Mutations of GJB2 and GJB6 genes are associated with deafness at the DFNB1 locus. The diagnosis of DFNB1 is made with molecular genetic testing. DNA-based testing can be used both prenatally and postnatally. Purpose: to get evidence for implementation of newborn hearing screening programs at national level;to use the molecular testing of children at risk for confirmation of diagnosis and early intervention. OAEs and ABR were performed for 4303 newborns. Audiologic evaluation of 38 children suspected of having hearing loss was performed too. Physical examinations and family history were used to get information about congenital deafness. DNA from blood samples was isolated, and two PCR multiplex assays were developed to detect DFNB1 mutations. Only 23 newborns were screened positive. Newborns were referred to audiologic evaluation, genetic counseling and testing for the etiologic diagnosis. Physical examination revealed no other abnormal findings. GJB2 mutations were detected in 36.03% of patients, and all of them have 35delG mutation. None of them was found to have GJB6 mutations. Our results suggested that molecular testing was an accurate method of early determining cause of congenital hearing loss and helped us to exclude GJB6 gene from the routine hearing screening protocol.
文摘Background The DFNB1 locus, which contains the gap junction beta-2 （GJB2） and gap junction beta-6 （GJB6） genes, plays a key role in the nonsyndromic and sporadic hearing impairment. Mutations of DFNB1 result in autosomaJ recessive nonsyndromic hearing impairment （ARNSHI）. Previous researches have identified mutations in GJB2 and GJB6, but single nucleotide polymorphisms （SNPs） of DFNB1 locus have not been studied. So we chose five SNPs to evaluate whether there is difference between deafness people and normal-hearing people in Han Chinese. Methods Five SNPs in the DFNB1 region were examined using a case-control association study between cases with sporadic hearing impairment and controls with normal hearing. The HWEsoft and SHEsis softwares were used to analyze the results. Results Single-locus association analysis showed a positive association for three SNPs： rs9315400, rs2274084 and 235delC. When we compared the distributions of the haplotypes, we also found significant differences between cases and controls in the haplotype combination of rs2274084 and rs2274083 （Х^2=12.978, df=3, global P=0.004719）. Conclusions The haplotypes composed of rs2274084 and rs2274083 suggested that C-C may be a risk haplotype for the sporadic hearing impairment while T-T may be protective against hearing impairment. From that point of view, we can conclude that the SNPs of DFNB1 locus also plays an important role in sporadic hearing impairment cases.
