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Genetic aetiology of ophthalmological manifestations in children – a focus on mitochondrial disease‐related symptoms
Author(s) -
Widgren Paula,
Hurme Anri,
Falck Aura,
KeskiFilppula Riikka,
Remes Anne M,
Moilanen Jukka,
Majamaa Kari,
Kervinen Marko,
Uusimaa Johanna
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.12897
Subject(s) - optic neuropathy , nystagmus , mitochondrial dna , medicine , retinopathy , compound heterozygosity , mitochondrial disease , nuclear dna , genetics , mutation , ophthalmology , gene , biology , optic nerve , diabetes mellitus , endocrinology , audiology
Abstract Purpose To investigate the association of mutations in the mitochondrial DNA (mt DNA ) 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 mt DNA and nuclear genes POLG 1 , OPA 1 and PEO 1 were analysed from the available DNA samples ( n = 38). Furthermore, some nuclear candidate genes were investigated based on family history and phenotype. Rare mt DNA mutations were evaluated using in silico predictors and sequence alignment. Results Three patients had previously identified mutations in mt DNA that are associated with optic neuropathy (in MT ‐ ND 6 and MT ‐ ND 1 ) and nystagmus (in tRNA Arg ). Nine rare mutations in MT ‐ ATP 6 were identified in seven patients, of whom four manifested with retinopathy and three had clusters of MT ‐ ATP 6 mutations. Nuclear PEO 1 and OPA 1 were unchanged in all samples, but a patient with nystagmus had a heterozygous POLG 1 mutation. The analysis of nuclear candidate genes revealed mutations in NDUF 8 (patient with nystagmus), TULP 1 (patient with optic neuropathy, nystagmus and retinopathy) and RP 2 (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 ‐ ATP 6 should be taken into account for children with retinopathy of unknown aetiology.