Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

Abstract

ObjectivesInfants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible.MethodsSix hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing.ResultsAmong the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G.ConclusionNewborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs.

Concurrent Hearing and Genetic Screening among Newborns in Ningbo, China

“…Thus, with cost-effective and rapid turnaround, the screening of large populations is feasible. Here, it should be noticed that the next-generation sequencing provides a stronger solution [ 10 , 14 ],whereas organizing massive population genetic screening is challenging, which also increases interpretation burden. In addition, the microarray platform shows excellent detection sensitivity to the heteroplasmic mitochondrial variants.…”

Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China

“…Studies have demonstrated the feasibility of concurrent hearing and genetic screening. [7][8][9][10][11] However, the benefits of such practices have not been quantified due to limited sample sizes and outcome data. Herein we report results of genetic screening on~1.2 million newborns in China and outcomes of 12,778 infants with genetic findings followed up via phone interviews.…”

Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China

“…Studies have demonstrated the feasibility of concurrent hearing and genetic screening. 7–11 However, the benefits of such practices have not been quantified due to limited sample sizes and outcome data. Herein we report results of genetic screening on ∼1.2 million newborns in China and outcomes of 12,778 infants with genetic findings followed-up via phone interviews.…”