Table 1.

Molecular Genetic Testing Used in Stickler Syndrome

Gene 1Proportion of Stickler Syndrome Attributed to Pathogenic Variants in GeneMOIProportion of Pathogenic Variants 2 Identified by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
COL2A1 ~80% 5AD~99%<1% 6
COL11A1 ~20% 5AD 7~99%<1% 6
COL11A2 <1% 6AD~100%None reported 6, 8
COL9A1 <1% 6AR~100%None reported 6, 8
COL9A2 <1% 6AR~100%None reported 6, 8
COL9A3 <1% 6AR~100%None reported 6, 8
Unknown 91%NANANA

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; NA = not applicable

1.
2.

See Molecular Genetics for information on variants detected in these genes.

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.

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.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

7.

Rarely, biallelic COL11A1 pathogenic variants have been reported in individuals with Stickler syndrome [Snead et al 2022]; in these instances, at least one pathogenic variant affects the alternatively spliced exon 9, and individuals have presented with more severe hearing loss [Richards et al 2013, Nixon et al 2020, Nixon et al 2022].

8.

To date, large exon or multiexon deletions or duplications in COL11A2, COL9A1, COL9A2, and COL9A3 have not been reported in individuals with Stickler syndrome.

9.

Pathogenic variants in BMP4, GZF1, LOXL3, and LRP2 have been reported in individuals with features overlapping those of Stickler syndrome (see Differential Diagnosis).

From: Stickler Syndrome

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