Two missense mutations in SLC26A4 gene: a molecular and functional study.

[pendred syndrome]

Mutations in the SLC 26 A 4 gene encoding pendrin , an anion transporter , are responsible for non-syndromic hearing loss (HL ) (DFNB 4 ) and Pendred syndrome (PS ). PS is a genetic disorder that causes early HL and affects the thyroid gland . Here , we report eight Tunisian families affected with profound HL . Clinical investigations revealed goiter in few patients . Genotyping using microsatellite makers showed linkage to SLC 26 A 4 , and missense mutations p .L 445 W and p .M 147 T were identified by sequencing and polymerase chain reaction-restriction fragment length polymorphism . The p .L 445 W mutation segregated in seven families and haplotype analysis suggested its founder effect . In order to understand the molecular pathogenic mechanisms of p .L 445 W and p .M 147 T mutations , SLC 26 A 4 wild-type and mutant cDNA constructs were transiently expressed in COS 7 cells and several human cell lines including Thyroid 8305 C cells . Reverse transcription-PCR , western blot and immunofluorescence demonstrated that these two mutations abolished complex glycosylation of pendrin and prevented its targeting to the plasma membrane .

Diseases
Validation

Diseases presenting "thyroid gland" symptom

familial hypocalciuric hypercalcemia

pendred syndrome

pleomorphic liposarcoma

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