Table 1.

Molecular Genetic Testing Used in Congenital Contractural Arachnodactyly

Gene 1Proportion of CCA Attributed to Pathogenic Variants in Gene 2MethodProportion of FBN2 Pathogenic Variants 3 Detectable by Method
FBN2 25%-75%Sequence analysis 4~93%
Gene-targeted deletion/duplication analysis 5~7% 6
Unknown25%-75%NA
1.

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

2.

Because the detection rate for FBN2 pathogenic or likely pathogenic variants is low in individuals with a clinically convincing diagnosis of CCA, genetic heterogeneity is likely [Gupta et al 2002; Nishimura et al 2007; Callewaert et al 2009; Meerschaut et al 2020; Callewaert et al, unpublished data].

3.

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

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or 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.

5.

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. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of an entire FBN2 deletion and/or deletion of adjacent genes (e.g., those described by Inbar-Feigenberg et al [2014]) may not be detected by these methods.

6.

Five known deletion/duplication pathogenic variants include a mosaic deletion of exons 7-34 [Lavillaureix et al 2017], a duplication of exon 23 [Gupta et al 2002], and a deletion of exons 38-48, 43-48, and 45-48 [Meerschaut et al 2020].

From: Congenital Contractural Arachnodactyly

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