Table 1.

Molecular Genetic Testing Used in Optic Atrophy Type 1

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
FamilialSimplex 3
OPA1 Sequence analysis 48/9 5
10/14 6
17/19 7
4/8 5
Gene-targeted deletion/duplication analysis 8Unknown 9Unknown
Targeted analysis for pathogenic variants 10UnknownUnknown
Unknown 11NA

See Molecular Genetics for information on variants detected in this gene.


Simplex = a single occurrence in a family


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Nakamura et al [2006] found heterozygous OPA1 pathogenic variants in 8/9 familial cases and 4/8 simplex cases. Of note, on examination of family members of two apparently simplex cases, Nakamura et al [2006] found heterozygous OPA1 pathogenic variants in relatives with a normal or only mildly abnormal phenotype, supporting the notions of variable expressivity and reduced penetrance.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


A ~325-bp intronic insertion resulting in exon skipping has been reported [Gallus et al 2010]. See Molecular Genetics.


Detects the Danish founder pathogenic c.2826delT variant. Note: Pathogenic variants included in a panel may vary by laboratory.


Because the detection rate for pathogenic variants in OPA1 is less than 100%, it is possible that families in which a pathogenic variant is not detected are not linked to the OPA1 locus; however, no evidence currently supports this possibility.


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