Table 1.

Molecular Genetic Testing Used in Xia-Gibbs Syndrome

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
AHDC1 Sequence analysis 397%-98% 4, 5
Gene-targeted deletion/duplication analysis 6Unknown 7, 8, 9
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. 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.

From Xia et al [2014], Yang et al [2015], Jiang et al [2018], Ritter et al [2018], Khayat et al [2021b], and data derived from DECIPHER [Firth et al 2009] and the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

5.

Most individuals so far reported have pathogenic truncating or missense variants in AHDC1.

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.

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

8.

There have been reports of large deletions of 1p36.11 that include AHDC1, with features overlapping with XGS. This accounts for up to 2%-3% of individuals identified with a pathogenic variant involving AHDC1. However, all known cases to date include adjacent genes as well, for which mutation can independently result in developmental disorders [Park et al 2017, Jiang et al 2018, Ritter et al 2018, Wang et al 2020].

9.

Deletions have been reported in the DECIPHER database, but the reported deletions are large and involve many genes, and there is not sufficient evidence to narrow down the cause to a single gene [Firth et al 2009]. Therefore, the evidence supporting the pathogenicity of AHDC1 deletions is incomplete and warrants further investigation.

From: Xia-Gibbs Syndrome

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