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

被引：37

作者：

Ansar, Muhammad ^{[1
]}

Ranza, Emmanuelle ^{[1
,2
]}

Shetty, Madhur ^{[3
]}

Paracha, Sohail A. ^{[4
]}

Azam, Maleeha ^{[5
]}

Kern, Ilse ^{[6
]}

Iwaszkiewicz, Justyna ^{[7
]}

Farooq, Omer ^{[8
]}

Pournaras, Constantin J. ^{[9
]}

Malcles, Ariane ^{[10
]}

Kecik, Mateusz ^{[10
]}

Rivolta, Carlo ^{[11
,12
,13
]}

Muzaffar, Waqar ^{[14
]}

Qurban, Aziz ^{[14
]}

Ali, Liaqat ^{[5
]}

Aggoun, Yacine ^{[15
]}

Santoni, Federico A. ^{[1
]}

Makrythanasis, Periklis ^{[1
]}

Ahmed, Jawad ^{[4
]}

Qamar, Raheel ^{[5
]}

Sarwar, Muhammad T. ^{[4
]}

Henry, L. Keith ^{[3
]}

Antonarakis, Stylianos E. ^{[1
,2
,16
]}

机构：

[1] Univ Geneva, Dept Genet Med & Dev, Geneva, Switzerland

[2] Univ Hosp Geneva, Serv Genet Med, Geneva, Switzerland

[3] Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND USA

[4] Khyber Med Univ, Inst Basic Med Sci, Peshawar, Pakistan

[5] COMSATS Univ, Fac Sci, Dept Biosci, Islamabad, Pakistan

[6] Geneva Univ Hosp, Childrens Hosp, Pediat Subspecialties Serv, Pediat Nephrol & Metab Unit, Geneva, Switzerland

[7] Univ Lausanne, Swiss Inst Bioinformat, Mol Modeling Grp, Lausanne, Switzerland

[8] Bahria Univ Med & Dent Coll, Karachi, Pakistan

[9] Hirslanden Clin La Colline, Geneva, Switzerland

[10] Univ Hosp Geneva, Dept Ophthalmol, Geneva, Switzerland

[11] Inst Mol & Clin Ophthalmol Basel IOB, Clin Res Ctr, Basel, Switzerland

[12] Univ Hosp Basel, Dept Ophthalmol, Basel, Switzerland

[13] Univ Leicester, Dept Genet & Genome Biol, Leicester, Leics, England

[14] Armed Forces Inst Ophthalmol, Rawalpindi, Pakistan

[15] Geneva Univ Hosp, Pediat Cardiol, Geneva, Switzerland

[16] iGE3 Inst Genet & Genom Geneva, Geneva, Switzerland

来源：

HUMAN MOLECULAR GENETICS | 2020年 / 29卷 / 04期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

CONE PHOTORECEPTORS;

D O I：

10.1093/hmg/ddz303

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 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.

引用

页码：618 / 623

页数：6

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