| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p35.3 | Optic atrophy 16 | 620629 | Autosomal recessive | 3 | MECR | 608205 |
A number sign (#) is used with this entry because of evidence that optic atrophy-16 (OPA16) is caused by homozygous mutation in the MECR gene (608205) on chromosome 1p35. One such family has been reported.
Optic atrophy-16 (OPA16) is an autosomal recessive disorder characterized by a Leber hereditary optic neuropathy (LHON)-like isolated optic neuropathy and mild sensorineural hearing impairment (Fiorini et al., 2023).
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Fiorini et al. (2023) reported 2 sibs with optic atrophy and mutation in the MECR gene. Patient 1 was diagnosed with low vision at 6 years of age and had progressive reduction in visual acuity with development of a central scotoma. She had 2 episodes of sudden painless vision loss at 28 and 44 years of age, followed by recovery of vision. Ophthalmologic examination at 44 years of age demonstrated small optic nerves with temporal pallor, and optical coherence tomography showed a reduction in the retinal nerve fiber layer. She also had a medical history of headaches since age 12 years, mild sensorineural hearing loss since age 45 years, and paroxysmal cardiac tachycardia since age 40 years. Patient 2 had sudden painless visual loss at 18 years of age with a slow recovery of vision. At 19 years of age, she had a bilateral central scotoma. Ophthalmologic examination at 34 years of age showed a color vision deficit and small optic discs with temporal pallor, and optical coherence tomography showed a diffuse reduction in the retinal nerve fiber layer. She had a history of headaches since age 14 years and mild sensorineural hearing loss since age 38 years.
The transmission pattern of optic atrophy-16 in the family reported by Fiorini et al. (2023) was consistent with autosomal recessive inheritance.
In 2 sibs with optic atrophy-16, Fiorini et al. (2023) identified homozygosity for a missense mutation in the MECR gene (R258W; 608205.0005). MECR protein expression was reduced in fibroblasts from the patients. Wildtype MECR and MECR with the R258W mutation were expressed in a yeast knockout for the etr1 gene (the ortholog of MECR) and protein expression of MECR with the R258W mutation was reduced compared to wildtype. In the etr1 yeast mutants, abnormal oxygen consumption and lipoylation of Lat1 and Kgd2 were normalized by expression of wildtype MECR but not MECR with the R258W mutation. Supplementation with lipoic acid improved Lat1 and Kgd2 lipoylation and growth after treatment with hydrogen peroxide in the mutant yeast expressing MECR with the R258W mutation.
Fiorini, C., Degiorgi, A., Cascavilla, M. L., Tropeano, C. V., La Morgia, C., Battista, M., Ormanbekova, D., Palombo, F., Carbonelli, M., Bandello, F., Carelli, V., Maresca, A., Barboni, P., Baruffini, E., Caporali, L. Recessive MECR pathogenic variants cause an LHON-like optic neuropathy. J. Med. Genet. 61: 93-101, 2023. [PubMed: 37734847] [Full Text: https://doi.org/10.1136/jmg-2023-109340]