Clinical and molecular analysis of three Mexican families with Pendred's syndrome.

Details

Serval ID
serval:BIB_87C5477EC2F8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Clinical and molecular analysis of three Mexican families with Pendred's syndrome.
Journal
European journal of endocrinology
Author(s)
Gonzalez Trevino O., Karamanoglu Arseven O., Ceballos C.J., Vives V.I., Ramirez R.C., Gomez V.V., Medeiros-Neto G., Kopp P.
ISSN
0804-4643 (Print)
ISSN-L
0804-4643
Publication state
Published
Issued date
06/2001
Peer-reviewed
Oui
Volume
144
Number
6
Pages
585-593
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney.
To perform a detailed clinical and molecular analysis of patients with Pendred's syndrome from four patients from three unrelated Mexican families.
Thyroid function tests, perchlorate test, thyroid scintigraphy, audiometry, computer tomography and magnetic resonance imaging were performed in all affected individuals. Haplotype analyses were performed using microsatellite markers flanking the PDS locus, and the PDS gene was submitted to direct sequence analysis.
All patients presented with sensorineural deafness, Mondini malformations of the cochlea, an enlarged vestibular aqueduct, goiter, and a positive perchlorate test. Two patients were hypothyroid, two individuals were euthyroid. Sequence analysis revealed a complex homozygous deletion/insertion mutation at the end of exon 4 in the index patient of family 1 resulting in a premature stop codon at position 138. In family 2, the affected individuals were compound heterozygous for a splice acceptor mutation (IVS2 -1G>A) and a 1231G>C transversion substituting alanine 411 by proline (A411P). In family 3, the index patient was found to be homozygous for a transversion 412G>T in exon 4 replacing valine 138 by phenylalanine (V138F).
All patients included in this study presented with the classic Pendred syndrome triad and molecular analysis revealed pendrin mutations as the underlying cause. The identification of three novel mutations, one of them of complex structure, expands the spectrum of mutations in the PDS gene and emphasizes that they display marked allelic heterogeneity.
Keywords
Adolescent, Child, Female, Goiter/genetics, Haplotypes, Hearing Loss, Sensorineural/genetics, Humans, Iodides/metabolism, Iodine/blood, Magnetic Resonance Imaging, Male, Metabolism, Inborn Errors/metabolism, Mutation/genetics, Pedigree, Reverse Transcriptase Polymerase Chain Reaction, Syndrome, Thyroid Hormones/blood, Tomography, X-Ray Computed
Pubmed
Web of science
Open Access
Yes
Create date
30/12/2020 15:03
Last modification date
31/12/2020 6:26
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