Table 1.

Molecular Genetic Testing Used in Hand-Foot-Genital Syndrome

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
HOXA13 Targeted testing for polyalanine repeat expansion 3~50%-60% 4
Sequence analysis 5~35% 4
Gene-targeted deletion/duplication analysis 6Unknown, none reported 7
Unknown 8NA
1.
2.

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

3.

PCR-based methods to identify HOXA13 expansion (resulting in increased polyalanine residues)

4.
5.

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.

6.

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.

7.

Other than in-frame contractions of polyalanine repeats, intragenic deletions causing HFGS that involve only part or all of HOXA13 have not been reported. Large deletions including HOXA13 and other surrounding genes have been reported [Devriendt et al 1999, Dunø et al 2004, Jun et al 2011, Pezzani et al 2015, Tas et al 2017]; however, these events result in additional clinical features (see Genetically Related Disorders).

8.

A few individuals with the clinical features of HFGS do not have HOXA13 pathogenic variants [Goodman et al 2000; Innis et al, unpublished].

From: Hand-Foot-Genital Syndrome

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