Table 1.

Summary of Molecular Genetic Testing Used in Leber Congenital Amaurosis

Gene
(Locus) 1
Proportion of LCA Attributed to Mutation of This GeneTest MethodVariants Detected 2
GUCY2D
(LCA1)
6%-21%Sequence analysis 3Sequence variants
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
RPE65
(LCA2)
3%-16%Sequence analysis 3Sequence variants
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
SPATA7
(LCA3)
UnknownSequence analysis 3Sequence variants
Sequence analysis 3 of select exons 7Sequence variants in exons 5,6,11,12
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
AIPL1
(LCA4)
4%-8%Sequence analysis 3Sequence variants
Sequence analysis 3 of select exons 7Sequence variants in exons 2-6
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
LCA5
(LCA5)
~1%-2%Sequence analysis 3Sequence variants
Sequence analysis 3 of select exons 7Sequence variants in exons 3,4,5,7 4
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication
RPGRIP1
(LCA6)
~5%Sequence analysis 3 of select exonsSequence variants
Sequence analysis 3 of select exons 4Sequence variants in selected exons
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
CRX
(LCA7)
~3%Sequence analysis 3Sequence variants
Sequence analysis 3 of select exons 4Sequence variants
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
Targeted analysis for pathogenic variantsSee footnote 4
CRB1
(LCA8)
UnknownSequence analysis 3Sequence variants
Sequence analysis 3 of select exons 4Sequence variants in selected exons
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 8
NMNAT1
(LCA9)
UnknownSequence analysis 3Sequence variants
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
CEP290
(LCA10)
≤20%Sequence analysis 3Sequence variants
Sequence analysis 3 of select exons 4Sequence variants in selected exons
Targeted analysis for pathogenic variants41-variant panel 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
IMPDH1
(LCA11)
Rare cause of dominant LCASequence analysis 3Sequence variants
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
RD3
(LCA12)
UnknownSequence analysis 3Sequence variants
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
RDH12
(LCA13)
~4%Sequence analysis 3Sequence variants
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
LRAT
(LCA14)
UnknownSequence analysis 3Sequence variants
Sequence analysis 3 of select exons 4Sequence variants in selected exons
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
TULP1
(LCA15)
UnknownSequence analysis 3Sequence variants
Sequence analysis 3 of select exons 4Sequence variants in exons 9,10,12,13,14
Targeted analysis for pathogenic variantsSee footnote 4
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
KCNJ13
(LCA16)
UnknownSequence analysis 3Sequence variants
Deletion/duplication analysis 5Partial- and whole-gene deletion/duplication 6
IQCB1UnknownSequence analysis 3Sequence variants
1.
2.

See Molecular Genetics for information on allelic variants.

3.

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

4.

Pathogenic variants in panel may vary.

5.

Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

6.

No deletions or duplications involving GUCY2D, AIPL1, CEP290, IMPDH1, LRAT, NMNAT1, RD3, RDH12, RPGRIP1, RPE65, SPATA7, CRX, or KCNJ13 have been reported to cause LCA.

7.

Exons sequenced may vary by laboratory.

8.

Whole-gene deletion reported [Stone 2007]

From: Leber Congenital Amaurosis

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