[A follow-up study of abnormal mutation in neonatal deafness gene screening]

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years' audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years' hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years' hearing follow-up. Conclusions: The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.