Government-funded universal newborn hearing screening and genetic analyses of deafness predisposing genes in Taiwan.
OBJECTIVE
To investigate the association of eight connexin genes (GJB2, GJB4, GJA1P1, GJB6, GJB3, GJA1, GJB1, and GJC3) and the SLC26A4 gene with congenital hearing impairment among infants in a universal newborn hearing screening program.


METHODS
From September 2009 to October 2013, the consecutive neonates born in all six branches of Taipei City Hospital were enrolled. Infants who failed the newborn hearing screening and were diagnosed with hearing impairment underwent the genetic analyses.


RESULTS
15,404 neonates were born at Taipei City Hospital, and 15,345 neonates underwent newborn hearing screening. Among them, 32 infants were diagnosed with unilateral or bilateral hearing impairment. 26 of them underwent analyses of the connexin genes and the SLC26A4 gene. Of the connexin genes, two infants carried a GJB3 mutation (heterozygous c.580G>A and heterozygous c.520G>A, respectively). Only one infant carried a GJB2 mutation (homozygous c.235delC). One infant carried a GJA1P1 mutation (heterozygous c.929delC) and another carried a GJB4 mutation (heterozygous c.302G>A). Additionally, one infant carried a GJA1P1 novel variant (heterozygous c.1081C>T). Another infant carried a GJA1 novel variant (heterozygous c.1-33C>G). Of the SLC26A4 gene, one infant carried heterozygous c.919-2A>G mutation and a novel variant (heterozygous c.164+1G>C), and high-resolution computed tomography (HRCT) of the temporal bone revealed bilateral enlarged vestibular aqueducts. One infant carried heterozygous c.919-2A>G mutation and no inner ear anomalies were demonstrated by HRCT of the temporal bone. Another infant carried a novel variant (heterozygous c.818C>T).


CONCLUSIONS
These results provide a genetic profile of the connexin genes and SLC26A4 gene among infants with hearing impairment detected by a universal newborn hearing screening program in Taiwan. Further studies and long-term follow up of this cohort are warranted to determine the pathogenicity of each variants and the long-term hearing consequence.
Department of Otolaryngology, Taipei City Hospital, Taipei, Taiwan.
Chun-Wei
CW
Chu
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Taipei City Hospital, Taipei, Taiwan; Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan.
Yann-Jang
YJ
Chen
Department of Otolaryngology, Taipei City Hospital, Taipei, Taiwan.
Yi-Hui
YH
Lee
Department of Medical Technology, Taipei City Hospital, Taipei, Taiwan.
Sian-Jang
SJ
Jaung
Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Fei-Peng
FP
Lee
Department of Otolaryngology, Taipei City Hospital, Taipei, Taiwan; Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: hmengh@yahoo.com.tw.
Hung-Meng
HM
Huang
D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006078:Government Programs; D034381:Hearing Loss / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D015997:Neonatal Screening; D000076988:Sulfate Transporters; D013624:Taiwan
D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26
Congenital hearing loss; Genetic testing; Newborn hearing screening