A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability.
Front. Genet.. 2015-10-19; 6:
DOI: 10.3389/fgene.2015.00311
Read on PubMed
1. Front Genet. 2015 Oct 19;6:311. doi: 10.3389/fgene.2015.00311. eCollection 2015.
A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with
mild intellectual disability.
Charif M(1), Roubertie A(2), Salime S(3), Mamouni S(4), Goizet C(5), Hamel CP(6),
Lenaers G(1).
Author information:
(1)Institut des Neurosciences de Montpellier, U1051 de l’INSERM, Université de
Montpellier Montpellier, France ; PREMMi, CNRS UMR 6214 – INSERM U1083,
Département de Biochimie et Génétique, Université d’Angers, CHU d’Angers Angers,
France.
(2)Institut des Neurosciences de Montpellier, U1051 de l’INSERM, Université de
Montpellier Montpellier, France ; CHRU Montpellier, Service de Neuro-pédiatrie,
Hôpital Gui de Chauliac Montpellier, France.
(3)Institut des Neurosciences de Montpellier, U1051 de l’INSERM, Université de
Montpellier Montpellier, France.
(4)CHRU Montpellier, Centre de Référence pour les Maladies Sensorielles
Génétiques, Hôpital Gui de Chauliac Montpellier, France.
(5)CHU Bordeaux, Service de Génétique Médicale and Université de Bordeaux,
Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM) Bordeaux, France.
(6)Institut des Neurosciences de Montpellier, U1051 de l’INSERM, Université de
Montpellier Montpellier, France ; CHRU Montpellier, Centre de Référence pour les
Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac Montpellier, France.
Dominant optic neuropathies causing fiber loss in the optic nerve are among the
most frequent inherited mitochondrial diseases. In most genetically resolved
cases, the disease is associated to a mutation in OPA1, which encodes an inner
mitochondrial dynamin involved in network fusion, cristae structure and
mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA
proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic
Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation
c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary
highly conserved arginine-finger motif, in a family with optic atrophy and mild
intellectual disability. Ophthalmic examinations disclosed a loss of retinal
nerve fibers on the temporal and nasal sides of the optic disk and a red-green
dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as
optic atrophy might be associated with AFG3L2 mutations, and should prompt the
screening of this gene in patients with isolated and syndromic inherited optic
neuropathies.
DOI: 10.3389/fgene.2015.00311
PMCID: PMC4609881
PMID: 26539208