Alu-element insertion in an OPA1 intron sequence associated with autosomal dominant optic atrophy

[摘要] Purpose: Autosomal dominant opticatrophy (ADOA) is the most common form of hereditary optic neuropathycaused by mutations in the optic atrophy 1 (OPA1) gene. It ischaracterized by insidious onset with a selective degeneration ofretinal ganglion cells, variable loss of visual acuity, temporal opticnerve pallor, tritanopia, and development of central, paracentral, orcecocentral scotomas. Here we describe the clinical and molecularfindings in a large Italian family with ADOA. Methods: Routine ophthalmologicexamination and direct sequencing of all coding regions of the OPA1gene were performed. Further characterization of a new OPA1gene insertion was performed by reverse transcription-PCR (RT–PCR) ofRNA from patients and control subjects. Results: We identified an Alu-elementinsertion located in intron 7 of OPA1 causing an in-framedeletion of exon 8 in 18 family members. Conclusions: The predicted consequenceof this mutation is the loss of the guanosine triphosphatase (GTPase)activity of OPA1. Alu insertions have been reported in the literatureas causing human genetic disease. However, this is the first report ofa pathogenic OPA1 gene mutation resulting from an Aluinsertion.

[学科分类] 生物化学/生物物理