Mutations in CLDN14 are associated with different hearing thresholds.
Mutations in CLDN14, encoding tight junction protein claudin 14, cause profound deafness in mice and humans. We identified a Pakistani family, in which the affected individuals were homozygous for a known pathogenic mutation c.254 T>A resulting in p.V85D substitution in CLDN14; however, in contrast to the previously reported families with mutations in CLDN14, most of the affected individuals in this family exhibit only a severe hearing loss (HL). In order to identify the contribution of CLDN14 to less than profound deafness, we screened for mutations of CLDN14 in 30 multiplex and 57 sporadic cases with moderately severe to severe HL from Pakistan. We identified one other affected individual homozygous for p.V85D substitution. Comparison of audiometric data from all patients indicates that mutations in CLND14 cause varying degrees of HL, which may be enhanced at high frequencies. This suggests that a modifier can reduce the severity of HL associated with mutations of CLDN14. Our data indicate that mutations in CLDN14 should be explored when considering the etiology of less severe HL.
Bashir
Rasheeda
R
School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
Fatima
Amara
A
Naz
Sadaf
S
D000293:Adolescent; D001299:Audiometry; D002648:Child; D057167:Claudins; D005190:Family; D005260:Female; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D012720:Severity of Illness Index; D055815:Young Adult
D057167:Claudins; D008565:Membrane Proteins; C422064:claudin 14
Hum Genet. 2000 Apr;106(4):399-405
10830906
Biochem Biophys Res Commun. 2009 Jul 17;385(1):1-5
19254696
Hum Mutat. 2005 Jun;25(6):543-9
15880785
Adv Otorhinolaryngol. 2002;61:156-60
12408079
Hum Mol Genet. 2003 Aug 15;12(16):2049-61
12913076
Hum Genet. 2008 Nov;124(4):357-68
18784943
Brain Res. 2006 May 26;1091(1):79-88
16579977
Genet Couns. 2005;16(3):309-11
16259330
Cell. 2001 Jan 12;104(1):165-72
11163249
Nat Genet. 2009 Aug;41(8):926-30
19561606
Clin Genet. 2003 Jul;64(1):65-9
12791041