Table 1.

Molecular Genetic Testing Used in Loeys-Dietz Syndrome

Gene 1Proportion of LDS Attributed to Pathogenic Variants in Gene 2Proportion of Pathogenic Variants 3 Detected by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
SMAD2 ~1%-5%90%-95%Unknown 6
SMAD3 ~5%-10%90%-95%Rare 7
TGFB2 ~5%-10%90%-95%Rare 8
TGFB3 ~1%-5%90%-95%Rare 9
TGFBR1 ~20%-25%~100%See footnote 10.
TGFBR2 ~55%-60%~100%See footnote 10.
Unknown 11NA

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


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.


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.


No data on gene-targeted del/dup analysis are available.


Deletion of TGFB3 has been observed [Author, personal communication].


Whole-gene deletion of TGFBR2 [Campbell et al 2011] or TGFBR1 [Redon et al 2006] and duplication of a 14.6-Mb region surrounding TGFBR1 [Breckpot et al 2010] have been reported; however, these individuals lacked aortic involvement. Several other persons with deletions of TGFBR1 or TGFBR2 have not developed aortic aneurysms to date, suggesting that at least some mutated protein needs to be present [Lindsay & Dietz 2011]. As such, whole deletion/duplication of TGFBR1 or TGFBR2 do not present with clear features of Loeys-Dietz syndrome. Smaller deletions/duplications that lead to in frame events are likely to cause an LDS phenotype, whereas events leading to out of frame are not.


Based on rare individuals with discriminating features of LDS who show no pathogenic variants in the known genes, additional LDS-associated genes remain to be identified [Authors, personal observation].

From: Loeys-Dietz Syndrome

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