Connexin gene mutations among Ugandan patients with nonsyndromic sensorineural hearing loss.
OBJECTIVE
Congenital deafness occurs in approximately 1 in 1,000 live births, and 50% of these cases are hereditary. Connexin mutations have been identified as the most common cause of hereditary hearing loss in many populations. The prevalence of this mutation in African patients has not been adequately studied. The objective of this study was to determine the prevalence of connexin 26 and 30 mutations in a population of hearing-impaired patients from Uganda.


METHODS
This is an observational study.


METHODS
Coding regions of both GJB2 and GJB6, noncoding exon 1 of GJB2, and 30 nucleotides of intronic sequence bordering the exons were analyzed in 126 subjects from Uganda with confirmed bilateral, severe-to-profound sensorineural hearing loss. All variants were analyzed for possible clinical significance using a combination of database searches and in silico tools.


RESULTS
Complete sequence data were obtained on 115/126 individuals; 11 had only partial or no results. Only one reported pathogenic variant was found in GJB2 (c.208C>G; p.Pro70Ala) and none in GJB6. Three reported variants and two novel variants within intron 1 of GJB2 and two variants within exon 3 of GJB6 were also found.


CONCLUSIONS
None of the most common types of deletions in the GJB2 gene (c.35delG, c.167delT or c.235delC) were found in this large cohort of deaf children from Uganda. This prompts a search for genetic causes of deafness among this and other previously studied African populations.
Department of Otolaryngology, Head and Neck Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.
Hedyeh
H
Javidnia
Nancy
N
Carson
Michael
M
Awubwa
Richard
R
Byaruhanga
David
D
Mack
Jean-Philippe
JP
Vaccani
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D015995:Prevalence; D014454:Uganda; D055815:Young Adult
D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26
African population; Sensorineural hearing loss; congenital hearing loss; connexin; genetic mutations