Table 1.

Molecular Genetic Testing Used in Generalized Arterial Calcification of Infancy (GACI)

Gene 1, 2Proportion of GACI Attributed to Pathogenic Variants in Gene 3, 4Proportion of Pathogenic Variants 5 Detectable by Method
Sequence
analysis 6		Gene-targeted deletion/duplication analysis 7
ABCC6 ~9%88% 812% 8
ENPP1 ~67%96% 84% 8
Unknown 9~24%NA
1.

Genes are listed in alphabetic order.

2.

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

3.
4.

While a majority of cases of GACI are caused by biallelic pathogenic variants in ENPP1, pathogenic variants in ABCC6 can cause a clinically indistinguishable phenotype.

5.

See Molecular Genetics for information on variants detected in these genes.

6.

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.

7.

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

8.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] and personal unpublished data

9.

22 of 92 individuals with GACI reported by Nitschke et al [2012] did not have biallelic pathogenic variants in either ENPP1 or ABCC6; however, two were heterozygous for an ENPP1 pathogenic variant, and six individuals in five unrelated families were heterozygous for an ABCC6 pathogenic variant.

From: Generalized Arterial Calcification of Infancy

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