Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency
Autor: | Constantin J. Pournaras, Emmanuelle Ranza, Jawad Ahmed, Aziz Qurban, Muhammad Ansar, Maleeha Azam, Omer Farooq, Mateusz Kecik, Sohail A. Paracha, Federico Santoni, Carlo Rivolta, Madhur Shetty, Raheel Qamar, Yacine Aggoun, Periklis Makrythanasis, Ilse Kern, Ariane Malclès, Waqar Muzaffar, Stylianos E. Antonarakis, Justyna Iwaszkiewicz, L. Keith Henry, Liaqat Ali, Muhammad T. Sarwar |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Retinal degeneration medicine.medical_specialty Taurine Cardiomyopathy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Taurine transporter ddc:590 Internal medicine Genetics medicine ddc:576.5 030212 general & internal medicine Molecular Biology Genetics (clinical) ddc:618 biology Membrane transport protein Transporter General Medicine medicine.disease Phenotype ddc:616.8 Transmembrane domain 030104 developmental biology Endocrinology chemistry Cone Photoreceptors biology.protein |
Zdroj: | Human Molecular Genetics, Vol. 29, No 4 (2020) pp. 618-623 |
ISSN: | 0964-6906 |
Popis: | 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. |
Databáze: | OpenAIRE |
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