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
1.

See Table A. Genes and Databases for chromosome locus and protein.

2.

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

3.

Simplex = a single occurrence in a family

4.

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.

5.

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.

6.
7.
8.

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.

9.

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

10.

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

11.

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.

From: Optic Atrophy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

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