Genetic aetiology of ophthalmological manifestations in children - a focus on mitochondrial disease-related symptoms.
Acta Ophthalmol
; 94(1): 83-91, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26448634
ABSTRACT
PURPOSE:
To investigate the association of mutations in the mitochondrial DNA (mtDNA) or nuclear candidate genes with mitochondrial disease-related ophthalmic manifestations (nystagmus, ptosis, ophthalmoplegia, optic neuropathy and retinopathy) in children.METHODS:
A retrospective cohort of children (n = 98) was identified from the medical record files of a tertiary care hospital. The entire mtDNA and nuclear genes POLG1, OPA1 and PEO1 were analysed from the available DNA samples (n = 38). Furthermore, some nuclear candidate genes were investigated based on family history and phenotype. Rare mtDNA mutations were evaluated using in silico predictors and sequence alignment.RESULTS:
Three patients had previously identified mutations in mtDNA that are associated with optic neuropathy (in MT-ND6 and MT-ND1) and nystagmus (in tRNA Arg). Nine rare mutations in MT-ATP6 were identified in seven patients, of whom four manifested with retinopathy and three had clusters of MT-ATP6 mutations. Nuclear PEO1 and OPA1 were unchanged in all samples, but a patient with nystagmus had a heterozygous POLG1 mutation. The analysis of nuclear candidate genes revealed mutations in NDUF8 (patient with nystagmus), TULP1 (patient with optic neuropathy, nystagmus and retinopathy) and RP2 (patient with retinopathy) genes.CONCLUSIONS:
Children with retinopathy, nystagmus or optic neuropathy, especially together with developmental delay or positive family history, should be considered for mitochondrial disease. MT-ATP6 should be taken into account for children with retinopathy of unknown aetiology.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
/
Doenças Mitocondriais
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Oftalmopatias
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Genoma Mitocondrial
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Mutação
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Acta Ophthalmol
Ano de publicação:
2016
Tipo de documento:
Article