Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes.

Details

Serval ID
serval:BIB_9C640F69BEF9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes.
Journal
The Journal of clinical endocrinology and metabolism
Author(s)
Pfarr N., Borck G., Turk A., Napiontek U., Keilmann A., Müller-Forell W., Kopp P., Pohlenz J.
ISSN
0021-972X (Print)
ISSN-L
0021-972X
Publication state
Published
Issued date
07/2006
Peer-reviewed
Oui
Volume
91
Number
7
Pages
2678-2681
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Pendred syndrome (PS) and thyroid peroxidase (TPO) deficiency are autosomal-recessive disorders that result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and an iodide organification defect as common features. Whereas the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses.
The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss, and PS was suspected.
We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro.
Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The mutant pendrin (p.R776C) retained its ability to transport iodide in vitro.
These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.
Keywords
Congenital Hypothyroidism/complications, Congenital Hypothyroidism/diagnosis, Congenital Hypothyroidism/genetics, Genotype, Goiter/complications, Goiter/genetics, Hearing Loss/complications, Hearing Loss/genetics, Heterozygote, Humans, Infant, Newborn, Iodide Peroxidase/genetics, Male, Membrane Transport Proteins/genetics, Mutation, Missense, Pedigree, Sulfate Transporters, Transfection
Pubmed
Web of science
Open Access
Yes
Create date
30/12/2020 14:25
Last modification date
31/12/2020 6:26
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