Segregation of a new mutation in SLC26A4 and p.E47X mutation in GJB2 within a consanguineous Tunisian family affected with Pendred syndrome.

[pendred syndrome]

Recessive mutations of the SLC 26 A 4 (PDS ) gene on chromosome 7 q 31 can cause sensorineural hearing loss with goiter (Pendred syndrome ) or non-syndromic autosomal recessive hearing loss (DFNB 4 ). Furthermore , mutations in the GJB 2 gene results in autosomal recessive (DFNB 1 ) and dominant (DFNA 3 ) non-syndromic hearing loss . The aim of the present study was to characterize a family with Pendred syndrome affected by severe to profound HL and presenting goiter .Affected members underwent detailed audiologic examination and characterization . DNA samples from family members were genotyped with polymorphic microsatellite markers and sequencing of the SLC 26 A 4 and GJB 2 genes was performed . A total of 25 families with non-syndromic hearing loss were screened for the common p .E 47 X mutation in the GJB 2 gene by direct dideoxy sequencing .Genetic microsatellite analysis showed linkage to the 7 q 22 -q 31 chromosomal region and mutation analysis revealed a novel frameshift mutation (c .451 delG ) in the SLC 26 A 4 gene . Screening of the GJB 2 gene in one patient , displayed a homozygous p .E 47 X mutation , together with a heterozygous c .451 delG mutation . Screening of 25 families with HL showed frequent segregation of the p .E 47 X mutation , which was homozygous in five of these families . Haplotype analysis using microsatellite markers and single nucleotide polymorphisms (SNPs ) closely flanking the GJB 2 gene , revealed the presence of two disease-associated-haplotypes suggesting the presence of at least , two founder effects carrying the p .E 47 X non-sense mutation in the Tunisian population .T he segregation of both SLC 26 A 4 and GJB 2 mutations in the family illustrates once again the unexpected intra-familial genetic heterogeneity in consanguineous families and highlights the difficulty of genetic counselling in such families . In addition , our results disclose the existence of founder effects in the Tunisian population .

Diseases
Validation

Diseases presenting "goiter" symptom

cowden syndrome

familial mediterranean fever

kabuki syndrome

pendred syndrome

This symptom has already been validated