Table 1.

Molecular Genetic Testing Used in Adams-Oliver Syndrome (AOS)

Gene 1Proportion of AOS Attributed to Pathogenic Variants in GeneMOIProportion of Pathogenic Variants 2 Detected by Method
Sequence analysis 3Gene-targeted deletion/
duplication analysis 4
ARHGAP31 <5% (2/47) 5AD≥99%Unknown 6
DLL4 ~9.9% (9/91) 7AD≥99%Unknown 6
DOCK6 ~17% (13/78) 8AR≥99%Unknown 9
EOGT <10% 10AR≥99%Unknown 6
NOTCH1 ~23% (17/74) 11, 12AD≥99%Unknown 13
RBPJ <10% 10, 14AD≥99%Unknown 6
Unknown40%-50% 5, 7, 10, 11, 12, 14, 15?NA

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance

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.

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.

5.
6.

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

7.
8.
9.

No data on detection rate of DOCK6 gene-targeted deletion/duplication analysis are available; however, one person with a deletion of exons 42-47 has been described [Sukalo et al 2015].

10.

Wim Wuyts, unpublished data

11.
12.
13.

No data on detection rate of NOTCH1 gene-targeted deletion/duplication analysis are available; however, one person with a heterozygous deletion has been described [Stittrich et al 2014].

14.
15.

The genetic cause has not been found in individuals with AOS and severe or lethal pulmonary hypertension [Author, personal observation; including in 2 such individuals in whom testing of the 6 known genes revealed no pathogenic variants].

From: Adams-Oliver Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

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