Clin Exp Otorhinolaryngol.  2015 Sep;8(3):211-217. 10.3342/ceo.2015.8.3.211.

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

• Li SX
• Chen DL
• Zhao SB
• Guo LL
• Feng HQ
• Zhang XF
• Ping LL
• Yang ZM
• Sun CX
• Yao GD

• KMID: 2117514
• DOI: http://doi.org/10.3342/ceo.2015.8.3.211

Abstract

OBJECTIVES
Infants 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.
METHODS
Six 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.
RESULTS
Among 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.
CONCLUSION
Newborn 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.

Keyword

Deafness; Cord Blood; Genes; High-Throughput Nucleotide Sequencing

MeSH Terms

Asian Continental Ancestry Group
China*
Deafness*
DNA, Mitochondrial
Fetal Blood
Gap Junctions
Genetic Testing
Hearing
Hearing Loss
Heterozygote
High-Throughput Nucleotide Sequencing
Homozygote
Humans
Infant
Infant, Newborn*
Mass Screening*
DNA, Mitochondrial

Figure

• 

  Fig. 1 Genotype mass spectra of mutational sites. (A) GJB2 c.235delC heterozygous mutation; (B) GJB2 p.R143W homozygous mutation; (C) GJB3 p.V84I heterozygous mutation; (D) GJB3 p.R180X heterozygous mutation; (E) SLC26A4 IVS7-2A>G heterozygous mutation; (F) SLC26A4 p.R409H heterozygous mutation. GJB2, gap junction beta-2 protein; GJB3, gap junction beta-3 protein; SLC26A4, solute carrier family 26 member 4. a, wild type; b, mutant type.

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