Table 1.

Molecular Genetic Testing Used in Autosomal Dominant Craniometaphyseal Dysplasia

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
ANKH Sequence analysis 3~90% 4
Gene-targeted deletion/duplication analysis 5None reported 6
Unknown 7NA~10%
1.

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

2.

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

3.

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.

4.
5.

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.

6.

Since AD-CMD occurs through a gain-of-function/dominant negative mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant.

7.

Some simplex cases of CMD did not have identifiable pathogenic variants in ANKH, suggesting possible locus heterogeneity.

From: Craniometaphyseal Dysplasia, Autosomal Dominant

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