Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency
Abstract 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 t...
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Published in | Human molecular genetics Vol. 29; no. 4; pp. 618 - 623 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
13.03.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Clinical Research Center, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland. These authors contributed equally. Present address: Biomedical Research Foundation of the Academy of Athens, Athens, Greece. Present address: Department of Endocrinology Diabetes and Metabolism, University Hospital of Lausanne, Lausanne, Switzerland. Present address: Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland. |
ISSN: | 0964-6906 1460-2083 |
DOI: | 10.1093/hmg/ddz303 |