Alu-element insertion in an OPA1 intron sequence associated with autosomal dominant optic atrophy.
OBJECTIVE
Autosomal dominant optic atrophy (ADOA) is the most common form of hereditary optic neuropathy caused by mutations in the optic atrophy 1 (OPA1) gene. It is characterized by insidious onset with a selective degeneration of retinal ganglion cells, variable loss of visual acuity, temporal optic nerve pallor, tritanopia, and development of central, paracentral, or cecocentral scotomas. Here we describe the clinical and molecular findings in a large Italian family with ADOA.


METHODS
Routine ophthalmologic examination and direct sequencing of all coding regions of the OPA1 gene were performed. Further characterization of a new OPA1 gene insertion was performed by reverse transcription-PCR (RT-PCR) of RNA from patients and control subjects.


RESULTS
We identified an Alu-element insertion located in intron 7 of OPA1 causing an in-frame deletion of exon 8 in 18 family members.


CONCLUSIONS
The predicted consequence of this mutation is the loss of the guanosine triphosphatase (GTPase) activity of OPA1. Alu insertions have been reported in the literature as causing human genetic disease. However, this is the first report of a pathogenic OPA1 gene mutation resulting from an Alu insertion.
Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, 53100 Siena, Italy.
Gian Nicola
GN
Gallus
Elena
E
Cardaioli
Alessandra
A
Rufa
Paola
P
Da Pozzo
Silvia
S
Bianchi
Camilla
C
D'Eramo
Michele
M
Collura
Manuela
M
Tumino
Lorenzo
L
Pavone
Antonio
A
Federico
D000293:Adolescent; D000328:Adult; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human