Mutation analysis of the SLC26A4, FOXI1 and KCNJ10 genes in individuals with congenital hearing loss.

[pendred syndrome]

Pendred syndrome (PDS ) and DFNB 4 comprise a phenotypic spectrum of sensorineural hearing loss disorders that typically result from biallelic mutations of the SLC 26 A 4 gene . Although PDS and DFNB 4 are recessively inherited , sequencing of the coding regions and splice sites of SLC 26 A 4 in individuals suspected to be affected with these conditions often fails to identify two mutations . We investigated the potential contribution of large SLC 26 A 4 deletions and duplications to sensorineural hearing loss (SNHL ) by screening 107 probands with one known SLC 26 A 4 mutation by Multiplex Ligation-dependent Probe Amplification (MLPA ). A heterozygous deletion , spanning exons 4 -6 , was detected in only one individual , accounting for approximately 1 % of the missing mutations in our cohort . This low frequency is consistent with previously published MLPA results . We also examined the potential involvement of digenic inheritance in PDS /DFNB 4 by sequencing the coding regions of FOXI 1 and KCNJ 10 . Of the 29 probands who were sequenced , three carried nonsynonymous variants including one novel sequence change in FOXI 1 and two polymorphisms in KCNJ 10 . We performed a review of prior studies and , in conjunction with our current data , conclude that the frequency of FOXI 1 (1 .4 %) and KCNJ 10 (3 .6 %) variants in PDS /DFNB 4 individuals is low . Our results , in combination with previously published reports , indicate that large SLC 26 A 4 deletions and duplications as well as mutations of FOXI 1 and KCNJ 10 play limited roles in the pathogenesis of SNHL and suggest that other genetic factors likely contribute to the phenotype .