Abstract:
:Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b. In addition, we screened a cohort of 19 unrelated patients with dominant optic atrophy by direct sequencing of the 30 OPA1 exons (including exons 4b and 5b) and found mutations in 17 (89%) of them of which 8 were novel. A majority of these mutations were truncative (65%) and located in exons 8 to 28, but a number of them were amino acid changes predominantly found in the GTPase domain (exons 8 to 15). We hypothesize that at least two modifications of OPA1 may lead to dominant optic atrophy, that is alteration in GTPase activity and loss of the last seven C-terminal amino acids that putatively interact with other proteins.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Delettre C,Griffoin JM,Kaplan J,Dollfus H,Lorenz B,Faivre L,Lenaers G,Belenguer P,Hamel CPdoi
10.1007/s00439-001-0633-ykeywords:
subject
Has Abstractpub_date
2001-12-01 00:00:00pages
584-91issue
6eissn
0340-6717issn
1432-1203journal_volume
109pub_type
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