Pendred's syndrome is an autosomal recessive disease characterized by goiter, 
impaired iodide organification, and congenital sensorineural deafness. The gene 
mutated in Pendred's syndrome, PDS (Pendred's syndrome gene), was cloned very 
recently and encodes the putative sulfate transporter pendrin. Pendred's 
syndrome may account for up to 10% of the cases with hereditary hearing loss, 
and pendrin mutations have also been found in a kindred with non-syndromic 
deafness. In this study, 41 individuals from a large, highly inbred pedigree 
from Northeastern Brazil were examined for features of Pendred's syndrome. 
Linkage studies and sequence analysis of the coding region of the PDS gene were 
performed with DNA from 36 individuals. The index patient, with the classical 
triad of deafness, positive perchlorate test, and goiter, was found to be 
homozygous for a deletion of thymidine 279 in exon 3, resulting in a frameshift 
and a premature stop codon at amino acid 96. This alteration resulted in 
truncation of the protein in the first transmembrane domain. Two other patients 
with deafness were found to be homozygous for this mutation; 19 were 
heterozygous and 14 were homozygous for the wild type allele. Surprisingly, 6 
deaf individuals in this kindred were not homozygous for the PDS gene mutation; 
3 were heterozygous and 3 were homozygous for the wild type allele, suggesting a 
probable distinct genetic cause for their deafness. All 3 homozygous individuals 
for the PDS mutation had goiters. However, goiters were also found in 10 
heterozygous individuals and in 6 individuals without the PDS mutation and are 
most likely caused by iodine deficiency. In conclusion, we identified a novel 
mutation in the PDS gene causing Pendred's syndrome. The comparison of phenotype 
and genotype reveals, however, that phenocopies generated by distinct 
environmental and/or genetic causes are present in this kindred and that the 
diagnosis of Pendred's syndrome may be difficult without molecular analysis.