Mitochondrial dynamics variation portal: the locus-specific databases portal of genes involved in mitochondrial dynamics
Pathogenic variants of the aconitase 2 gene (ACO2; MIM# 100850) are responsible for a broad clinical spectrum involving optic nerve degeneration, ranging from isolated optic neuropathy with recessive or dominant inheritance, to complex neurodegenerative syndromes with recessive transmission.
Reference:
Guehlouz, K. et al. ACO2 clinicobiological dataset with extensive phenotype ontology annotation. Scientific Data 8, https://doi.org/10.1038/s41597-021-00984-x (2021).
Pathogenic variants of the nuclear receptor subfamily 2 group F member 1 gene (NR2F1; MIM# 132890) are responsible for Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; MIM# 615722), an autosomal dominant disorder characterized by optic atrophy associated with developmental delay and intellectual disability.
Reference:
Billiet, B. et al. NR2F1 database: 112 variants and 84 patients support refining the clinical synopsis of Bosch-Boonstra-Schaaf optic atrophy syndrome. Hum Mutat, https://doi.org/10.1002/humu.24305 (2021).
Mutations in the optic atrophy 1 gene (OPA1; MIM# 605290) are responsible for about 60-80% of the cases of autosomal dominant optic atrophy (DOA, Kjer type; MIM# 165500; characterized by moderate to severe loss of visual acuity, blue-yellow dyschromatopsia and central scotoma). The spectrum of OPA1-related disorders is highly variable. The age of onset varies from birth to over 60 years, and the severity of the visual loss ranges from subclinical loss to severe blindness. Extra ocular features, involving the central, peripheral and autonomous nervous systems, complicating the optic neuropathy are reported in about 20% of the patients carrying OPA1 pathogenic variants, leading to conditions described as the "DOA plus" or "DOA+" syndromes (MIM# 125250). A phenotype fully compatible with the Behr syndrome (MIM# 210000), associating early onset and severe optic neuropathy with spinocerebellar ataxia and retarded development was also reported.
References:
Ferre, M., Amati-Bonneau, P., Tourmen, Y., Malthiery, Y. & Reynier, P. eOPA1: an online database for OPA1 mutations. Hum Mutat 25, 423-428, https://doi.org/10.1002/humu.20161 (2005).
Ferre, M. et al. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data. Hum Mutat 36, 20-25, https://doi.org/10.1002/humu.22703 (2015).
Le Roux, B. et al. OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database. Orphanet journal of rare diseases 14, 214, https://doi.org/10.1186/s13023-019-1187-1 (2019).
The Reticulon 4 interacting protein 1 gene (RTN4IP1; MIM# 610502) is located on chromosome 6q21 and includes 9 translated exons encoding Reticulon-4-interacting protein 1, mitochondrial (RTN4IP1; Swiss-Prot:RT4I1_HUMAN), a mitochondrial targeted protein with a quinone oxidoreductase activity.
References:
Rocatcher, A. et al. (under submission)
The single-stranded DNA binding protein 1 gene (SSBP1; MIM# 600439) located on chromosome 7q34 is a housekeeping gene whose canonical transcription variant, numbered 5, contains 7 exons. It encodes the 148 amino acids (aa) of the mitochondrial single-stranded DNA-binding protein (Mt-SSB; Swiss-Prot: SSBP_HUMAN), with 4 other potential isoforms ranging from 28 to 135 aa (TrEMBL:C9J8J0_HUMAN, C9K0U8_HUMAN, A0A0G2JLD8_HUMAN, E7EUY5_HUMAN), involved in mitochondrial biogenesis, including mtDNA replication and maintenance. It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability.
Recently, variants in SSBP1 are responsible for optic atrophy 13 with retinal and foveal abnormalities (OPA13; MIM# 165510), an autosomal dominant disorder characterized by decreased visual acuity due to bilateral optic atrophy. In addition, most patients develop retinal pigmentary involvement and abnormal appearance of the fovea, and may also have difficulties with colour vision. Some patients may develop additional systemic features, including sensorineural deafness and progressive nephropathy resulting in renal failure. Most pathogenic variants are familial and dominant, with some rare de novo cases or biallelic variants or potentially associated with a mitochondrial variant.
Recently, variants in SSBP1 are responsible for optic atrophy 13 with retinal and foveal abnormalities (OPA13; MIM# 165510), an autosomal dominant disorder characterized by decreased visual acuity due to bilateral optic atrophy. In addition, most patients develop retinal pigmentary involvement and abnormal appearance of the fovea, and may also have difficulties with colour vision. Some patients may develop additional systemic features, including sensorineural deafness and progressive nephropathy resulting in renal failure. Most pathogenic variants are familial and dominant, with some rare de novo cases or biallelic variants or potentially associated with a mitochondrial variant.
References:
Selhane, M. et al. (work in progress)
About us
We are an academic research team of the Mitovasc - CNRS 6015/Inserm 1083 research unit specialized in disorders involving mitochondrial dynamics and bioenergetics, headed by Dr. Guy Lenaers. Our main building is located in Angers, France, at the edges of the River Maine.
Who supports us
In France, academic research can have multiple affiliations. Here are ours: CNRS (National Center for Scientific Research), a government-funded research organization, under the administrative authority of France’s Ministry of Research; Inserm (French National Institute of Health and Medical Research), a public scientific and technological institute which operates under the joint authority of the French Ministry of Health and French Ministry of Research; University Hospital of Angers, that provide clinical education and training to future and current doctors, nurses, and other health professionals, in addition to delivering medical care to patients; University of Angers, committed to seeking continual improvement in teaching methods, and new technologies play a key role.
We bring positive and energetic relationships with the patients’ associations. We are grateful to (by alphabetic order): Association contre les Maladies Mitochondriales, Fondation Visio, Kjer France, Ouvrir les Yeux, Retina France and Union Nationale des Aveugles et Déficients Visuels.
We bring positive and energetic relationships with the patients’ associations. We are grateful to (by alphabetic order): Association contre les Maladies Mitochondriales, Fondation Visio, Kjer France, Ouvrir les Yeux, Retina France and Union Nationale des Aveugles et Déficients Visuels.