title: Differential diagnosis between Pendred and pseudo-Pendred syndromes: clinical, radiologic, and molecular studies.
abstract: The disease gene for Pendred syndrome has been recently characterized and named PDS. It codes for a transmembrane protein called pendrin, which is highly expressed at the apical surface of the thyroid cell and functions as a transporter of chloride and iodide. Pendrin is also expressed at the inner ear level, where it appears to be involved in the maintenance of the endolymph homeostasis in the membranous labyrinth, and in the kidney, where it mediates chloride-formate exchange and bicarbonate secretion. Mutations in the PDS gene and the consequent impaired function of pendrin leads to the classic phenotype of Pendred syndrome, i.e. dyshormonogenic goiter and congenital sensorineural hearing loss. In the present study, we performed a detailed clinical, radiologic, and molecular analysis of six families presenting with clinical diagnosis of Pendred syndrome. In two families a homozygous pattern for PDS mutations was found, whereas the affected members of the other four families were compound heterozygotes. One family did not harbor PDS mutations. Among the four novel mutations described, one is a transversion in exon 2 (84C>A), leading to the substitution S28R. Two other novel mutations lie in exon 4 (398T>A) and in exon 16 (1790T>C), leading to the substitutions S133T and L597S, respectively. The fourth novel mutation (1614+1G>A) is located in the first base pair of intron 14, probably affecting the splicing of the PDS gene. Clinically, all patients had goiter with positive perchlorate test, hypothyroidism, and severe or profound sensorineural hearing loss. In all the individuals harboring PDS mutations, but not in the family without PDS mutations, inner ear malformations, such as enlargement of the vestibular aqueduct and of the endolymphatic duct and sac, were documented. The pseudo-Pendred phenotype exhibited by the family without PDS mutations is likely caused by an autoimmune thyroid disease associated with a sensorineural hearing loss of different origin.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Nadia
authors.initials: N
authors.lastname: Cerutti
authors.forename: Deborah
authors.initials: D
authors.lastname: Mannavola
authors.forename: Antonino
authors.initials: A
authors.lastname: Crino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassio
authors.forename: Pietro
authors.initials: P
authors.lastname: Gasparoni
authors.forename: Guia
authors.initials: G
authors.lastname: Vannucchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D007758:Ear, Inner / Q000473:pathology*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis* / Q000235:genetics; D007558:Italy; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D000076988:Sulfate Transporters; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters