Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).
Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.
Everett
L A
LA
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glaser
B
B
Beck
J C
JC
Idol
J R
JR
Buchs
A
A
Heyman
M
M
Adawi
F
F
Hazani
E
E
Nassir
E
E
Baxevanis
A D
AD
Sheffield
V C
VC
Green
E D
ED
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000076988:Sulfate Transporters; D013431:Sulfates / Q000378:metabolism*; D013577:Syndrome
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D013431:Sulfates