Table 1.

Molecular Genetic Testing Used in SOST-Related Sclerosing Bone Dysplasias

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
SclerosteosisVan Buchem disease
SOST Sequence analysis 3100% 4None reported
Targeted deletion analysis for 52-kb del downstream of SOST 5None reported100% 6
1.

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

2.

See Molecular Genetics for information on 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 missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

SOST pathogenic variants were identified on sequence analysis in 94 of 96 individuals with sclerosteosis; two individuals did not undergo molecular testing and were diagnosed based on clinical and radiographic features [van Lierop et al 2017]. Note: Sixty-six of the 94 individuals who underwent molecular testing were homozygous for the South African founder variant c.70C>T (p.Gln24Ter).

5.

Targeted deletion analysis 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 the 52-kb deletion downstream of SOST.

6.

A homozygous 52-kb deletion downstream of SOST, which does not overlap the coding region, has been described in all Dutch individuals with van Buchem disease and the two affected individals from Germany [Balemans et al 2002, Staehling-Hampton et al 2002, van Lierop et al 2017].

From: SOST-Related Sclerosing Bone Dysplasias

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