编码线粒体动力相关蛋白的核基因OPA1在显性遗传性视神经萎缩中发生突变。

Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.

作者信息

Delettre C, Lenaers G, Griffoin J M, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel C P

机构信息

Inserm U. 254, Laboratoire de Neurobiologie de l'audition, Montpellier, France.

出版信息

Nat Genet. 2000 Oct;26(2):207-10. doi: 10.1038/79936.

DOI:10.1038/79936

PMID:11017079

Abstract

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals that features progressive loss in visual acuity leading, in many cases, to legal blindness. Phenotypic variations and loss of retinal ganglion cells, as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment. The OPA1 gene has been localized to 3q28-q29 (refs 13-19). We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology.

摘要

1型视神经萎缩（OPA1，MIM 165500）是一种常染色体显性遗传性视神经病变，发病率为五万分之一，其特征是视力逐渐丧失，在许多情况下会导致法定失明。如在Leber遗传性视神经病变（LHON）中发现的表型变异和视网膜神经节细胞丢失，提示可能存在线粒体损伤。OPA1基因已被定位到3q28-q29（参考文献13 - 19）。我们在此描述一个位于候选区域内的核基因OPA1，它编码一种定位于线粒体的发动蛋白相关蛋白。我们发现四个不同的OPA1突变，包括移码突变和错义突变，与该疾病共分离，证明线粒体在视网膜神经节细胞病理生理学中发挥作用。