Pendred syndrome is a recessive inherited disorder that consists of 
developmental abnormalities of the cochlea, sensorineural hearing loss, and 
diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of 
cases of hereditary deafness. The disease gene (PDS) has been mapped to 
chromosome 7q22-q31, and encodes a chloride-iodide transport protein. We 
performed mutation analysis of individual exons of the PDS gene in one Spanish 
family that shows intrafamilial variability of the deafness phenotype (two 
patients with profound and one with moderate-severe deafness). We identified a 
new splice-site mutation affecting intron 4 of the PDS gene, at nucleotide 
position 639+7. RNA analysis from lymphocytes of the affected patients showed 
that mutation 639+7A-->G generates a new donor splice site, leading to an mRNA 
with an insertion of six nucleotides from intron 4 of PDS. Since the newly 
created donor splice site is likely to compete with the normal one, variations 
of the levels of normal and aberrant transcripts of the PDS gene in the cochlea 
may explain the variability in the deafness presentation.