Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.

Détails

ID Serval
serval:BIB_7146D72E2133
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.
Périodique
Human molecular genetics
Auteur(s)
Ansar M., Ranza E., Shetty M., Paracha S.A., Azam M., Kern I., Iwaszkiewicz J., Farooq O., Pournaras C.J., Malcles A., Kecik M., Rivolta C., Muzaffar W., Qurban A., Ali L., Aggoun Y., Santoni F.A., Makrythanasis P., Ahmed J., Qamar R., Sarwar M.T., Henry L.K., Antonarakis S.E.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
13/03/2020
Peer-reviewed
Oui
Volume
29
Numéro
4
Pages
618-623
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In a consanguineous Pakistani family with two affected individuals, a homozygous variant Gly399Val in the eighth transmembrane domain of the taurine transporter SLC6A6 was identified resulting in a hypomorph transporting capacity of ~15% compared with normal. Three-dimensional modeling of this variant has indicated that it likely causes displacement of the Tyr138 (TM3) side chain, important for transport of taurine. The affected individuals presented with rapidly progressive childhood retinal degeneration, cardiomyopathy and almost undetectable plasma taurine levels. Oral taurine supplementation of 100 mg/kg/day resulted in maintenance of normal blood taurine levels. Following approval by the ethics committee, a long-term supplementation treatment was introduced. Remarkably, after 24-months, the cardiomyopathy was corrected in both affected siblings, and in the 6-years-old, the retinal degeneration was arrested, and the vision was clinically improved. Similar therapeutic approaches could be employed in Mendelian phenotypes caused by the dysfunction of the hundreds of other molecular transporters.
Mots-clé
Adolescent, Biological Transport, Cardiomyopathies/drug therapy, Cardiomyopathies/metabolism, Cardiomyopathies/pathology, Child, Female, Humans, Male, Membrane Glycoproteins/deficiency, Membrane Transport Proteins/deficiency, Pedigree, Retinal Degeneration/drug therapy, Retinal Degeneration/metabolism, Retinal Degeneration/pathology, Taurine/therapeutic use
Pubmed
Web of science
Création de la notice
25/02/2020 17:48
Dernière modification de la notice
17/06/2021 5:35
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