Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies

被引：55

作者：

Angebault, Claire ^{[1
,12
]}

Guichet, Pierre-Olivier ^{[1
,12
]}

Talmat-Amar, Yasmina ^{[1
,12
]}

Charif, Majida ^{[1
,2
,13
]}

Gerber, Sylvie ^{[3
,13
]}

Fares-Taie, Lucas ^{[3
,13
]}

Gueguen, Naig ^{[2
]}

Halloyn, Francois ^{[1
]}

Moore, David ^{[4
]}

Amati-Bonneau, Patrizia ^{[2
]}

Manes, Gael ^{[1
]}

Hebrard, Maxime ^{[1
]}

Bocquet, Beatrice ^{[5
]}

Quiles, Melanie ^{[1
]}

Piro-Megy, Camille ^{[1
]}

Teigell, Marisa ^{[1
]}

Delettre, Cecile ^{[1
]}

Rossel, Mireille ^{[6
]}

Meunier, Isabelle ^{[1
,5
]}

Preising, Markus ^{[7
]}

Lorenz, Birgit ^{[7
]}

Carelli, Valerio ^{[8
,9
]}

Chinnery, Patrick F. ^{[4
]}

Yu-Wai-Man, Patrick ^{[4
,10
]}

Kaplan, Josseline ^{[3
]}

Roubertie, Agathe ^{[1
,5
]}

Barakat, Abdelhamid ^{[11
]}

Bonneau, Dominique ^{[2
]}

Reynier, Pascal ^{[2
]}

Rozet, Jean-Michel ^{[3
]}

Bomont, Pascale ^{[1
]}

Hamel, Christian P. ^{[1
,5
]}

Lenaers, Guy ^{[1
,2
]}

机构：

[1] Univ Montpellier, Inst Neurosci Montpellier, INSERM U1051, F-34090 Montpellier, France

[2] Univ LUNAM, Dept Biochimie & Genet, CNRS 6214, INSERM U1083, F-49933 Angers, France

[3] Ctr Hosp Univ, F-49933 Angers, France

[4] Hop Necker Enfants Malad, INSERM U1163, F-75015 Paris, France

[5] Newcastle Univ, Ctr Life, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[6] Wellcome Trust Ctr Mitochondrial Res, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[7] CHRU Montpellier, Hop Gui Chauliac, Ctr Reference Malad Sensorielles Genet, F-34090 Montpellier, France

[8] INSERM U710, Lab MMDN EPHE, F-34090 Montpellier, France

[9] Univ Giessen, Dept Ophthalmol, D-35392 Giessen, Germany

[10] Bellaria Hosp, IRCCS, Inst Neurol Sci Bologna, I-40139 Bologna, Italy

[11] Univ Bologna, Dept Biomed & NeuroMotor Sci, I-40139 Bologna, Italy

[12] Royal Victoria Infirm, Newcastle Eye Ctr, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[13] Inst Pasteur Maroc, Dept Rech Sci, Lab Genet Mol Humaine, Casablanca 20360, Morocco

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2015年 / 97卷 / 05期

关键词：

MITOCHONDRIAL PROTEIN; ATROPHY; NOGO; OPA1; IDENTIFICATION; REGENERATION;

D O I：

10.1016/j.ajhg.2015.09.012

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Autosomal-recessive optic neuropathies are rare blinding conditions related to retinal ganglion cell (RGC) and optic-nerve degeneration, for which only mutations in TMEM126A and ACO2 are known. In four families with early-onset recessive optic neuropathy, we identified mutations in RTN4IP1, which encodes a mitochondrial ubiquinol oxydo-reductase. RTN4IP1 is a partner of RTN4 (also known as NOGO), and its ortholog Rad8 in C. elegans is involved in UV light response. Analysis of fibroblasts from affected individuals with a RTN4IP1 mutation showed loss of the altered protein, a deficit of mitochondrial respiratory complex I and IV activities, and increased susceptibility to UV light. Silencing of RTN4IP1 altered the number and morphogenesis of mouse RGC dendrites in vitro and the eye size, neuro-retinal development, and swimming behavior in zebrafish in vivo. Altogether, these data point to a pathophysiological mechanism responsible for RGC early degeneration and optic neuropathy and linking RTN4IP1 functions to mitochondrial physiology, response to UV light, and dendrite growth during eye maturation.

引用

页码：754 / 760

页数：7

共 26 条

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[Anonymous], J GUANGXI AGR MECHAN

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