Phenocopies for deafness and goiter development in a large inbred Brazilian kindred with Pendred's syndrome associated with a novel mutation in the PDS gene.

Détails

ID Serval
serval:BIB_17C81B5354F7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phenocopies for deafness and goiter development in a large inbred Brazilian kindred with Pendred's syndrome associated with a novel mutation in the PDS gene.
Périodique
The Journal of clinical endocrinology and metabolism
Auteur⸱e⸱s
Kopp P., Arseven O.K., Sabacan L., Kotlar T., Dupuis J., Cavaliere H., Santos C.L., Jameson J.L., Medeiros-Neto G.
ISSN
0021-972X (Print)
ISSN-L
0021-972X
Statut éditorial
Publié
Date de publication
01/1999
Peer-reviewed
Oui
Volume
84
Numéro
1
Pages
336-341
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
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.
Mots-clé
Adult, Brazil, Carrier Proteins/genetics, DNA/chemistry, Deafness/genetics, Female, Genetic Linkage, Genotype, Goiter/genetics, Humans, Male, Membrane Transport Proteins, Mutation, Phenotype, Sulfate Transporters, Syndrome
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/12/2020 15:26
Dernière modification de la notice
31/12/2020 6:26
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