دورية أكاديمية
Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.
| العنوان: | Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. |
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| المؤلفون: | Ansar M; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland., Ranza E; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.; Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland., Shetty M; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA., Paracha SA; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Azam M; Department of Biosciences, Faculty of Science, COMSATS University, Islamabad, Pakistan., Kern I; Pediatric Nephrology and Metabolism Unit, Pediatric Subspecialties Service, Children's Hospital, Geneva University Hospitals, Geneva, Switzerland., Iwaszkiewicz J; Swiss Institute of Bioinformatics, Molecular Modeling Group, University of Lausanne, Lausanne, Switzerland., Farooq O; Bahria University Medical and Dental College, Karachi, Pakistan., Pournaras CJ; Hirslanden Clinique La Colline, Geneva, Switzerland., Malcles A; Department of Ophthalmology, University Hospitals of Geneva, Geneva, Switzerland., Kecik M; Department of Ophthalmology, University Hospitals of Geneva, Geneva, Switzerland., Rivolta C; Clinical Research Center, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.; Department of Ophthalmology, University Hospital Basel, Switzerland.; Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom., Muzaffar W; Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan., Qurban A; Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan., Ali L; Department of Biosciences, Faculty of Science, COMSATS University, Islamabad, Pakistan., Aggoun Y; Pediatric Cardiology, Geneva University Hospitals, Geneva, Switzerland., Santoni FA; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland., Makrythanasis P; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland., Ahmed J; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Qamar R; Department of Biosciences, Faculty of Science, COMSATS University, Islamabad, Pakistan., Sarwar MT; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Henry LK; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA., Antonarakis SE; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.; Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.; iGE3 Institute of Genetics and Genomics of Geneva, Geneva, Switzerland. |
| المصدر: | Human molecular genetics [Hum Mol Genet] 2020 Mar 13; Vol. 29 (4), pp. 618-623. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992- |
| مواضيع طبية MeSH: | Cardiomyopathies/*drug therapy , Membrane Glycoproteins/*deficiency , Membrane Transport Proteins/*deficiency , Retinal Degeneration/*drug therapy , Taurine/*therapeutic use, Adolescent ; Biological Transport ; Cardiomyopathies/metabolism ; Cardiomyopathies/pathology ; Child ; Female ; Humans ; Male ; Pedigree ; Retinal Degeneration/metabolism ; Retinal Degeneration/pathology |
| مستخلص: | 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. (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) |
| التعليقات: | Comment in: Eur J Hum Genet. 2020 Nov;28(11):1479-1480. (PMID: 32572200) |
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| معلومات مُعتمدة: | R01 DA027845 United States DA NIDA NIH HHS |
| المشرفين على المادة: | 0 (Membrane Glycoproteins) 0 (Membrane Transport Proteins) 148686-53-7 (taurine transporter) 1EQV5MLY3D (Taurine) |
| تواريخ الأحداث: | Date Created: 20200107 Date Completed: 20210603 Latest Revision: 20210615 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7068170 |
| DOI: | 10.1093/hmg/ddz303 |
| PMID: | 31903486 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2083 |
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| DOI: | 10.1093/hmg/ddz303 |