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

Details

Serval ID
serval:BIB_7146D72E2133
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency
Journal
Hum Mol Genet
Author(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
0964-6906
Publication state
Published
Issued date
2019
Language
english
Notes
1460-2083
Ansar, Muhammad
Ranza, Emmanuelle
Shetty, Madhur
Paracha, Sohail A
Azam, Maleeha
Kern, Ilse
Iwaszkiewicz, Justyna
Farooq, Omer
Pournaras, Constantin J
Malcles, Ariane
Kecik, Mateusz
Rivolta, Carlo
Muzaffar, Waqar
Qurban, Aziz
Ali, Liaqat
Aggoun, Yacine
Santoni, Federico A
Makrythanasis, Periklis
Ahmed, Jawad
Qamar, Raheel
Sarwar, Muhammad T
Henry, L Keith
Antonarakis, Stylianos E
Journal Article
England
Hum Mol Genet. 2019 Dec 31. pii: 5691205. doi: 10.1093/hmg/ddz303.
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.
Create date
25/02/2020 18:48
Last modification date
26/02/2020 7:26
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