Table 3.

Molecular Genetic Testing Used in CLCN7-Related Osteopetrosis

Gene 1Test MethodProportion of Probands with a Pathogenic Variant 2 Detectable by This Method
CLCN7Sequence analysis 3~95% 4
Gene-targeted deletion/duplication analysis 5Unknown 6, 7
1.
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. 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.

Virtually all pathogenic variants reported in the literature have been identified by sequencing of the gene, the majority by classical Sanger sequencing, more recently also by exome or gene panel-based sequencing [Author, personal observation].

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used can 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.

Example of homozygous 101-kb contiguous gene deletion including exons 7-25 of CLCN7 [Pangrazio et al 2012]

7.

No data on detection rate of gene-targeted deletion/duplication analysis are available.

From: CLCN7-Related Osteopetrosis

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