Table 2. Kniest dysplasia associated COL2A1 variants reported here and elsewhere.
| COL2A1 sequence variant | Number of unrelated patients (comment) | Likely effect on COL2A1 mRNA and/or protein | References |
|---|---|---|---|
| c.905C>T, p.Ala302Val | 7 (mutation not identified in either parent in 2 cases) | Creation of a cryptic splice-donor site within exon 14 leading to a 21-bp deletion;22, 23 skipping of exon 14.29 | 8, 22, 23, 30, 31, 32 |
| c.906_924+9delGGGTGCTCCTGGTGTGAAGGTGAGAGGC | 2 (mother of one of these patients is somatic mosaic and has milder disease) | 28-bp deletion containing junction of exon 14 and intron 14 leading to exon skipping and a 54-bp deletion.3 | 3, 7, 16, 33 |
| c.908G>A, p.Gly303Asp | 1 (mutation not identified in either parent) (patient reported to later develop a SEDC phenotype)15 | Predicted not to have a clear effect on splicing.34 | 35 |
| c.980G>A, p.Gly327Asp | 1 (case only mentioned as ‘unpublished work') | Predicted to alter a splice enhancer element in exon 16.34 | 35, 36 |
| c.1023+1G>T | 1 | Misplicing of exon 16.8 | 8 |
| c.1023+1_1023+4delGTGA | 1 | Skipping of exon 16 leading to an 18-bp deletion.16 | 16 |
| c.1023+2T>G | 1 | Misplicing of exon 16.13 | 13 |
| c.1024-2A>C | 1 (mutation not identified in either parent) | Skipping of exon 17.37 | 37 |
| c.1068+1G>A | 1 (severe disease; patient died at week 2) | Skipping of exon 17 leading to a 45-bp deletion.36 | 36 |
| c.1076_1096delTCGGTCCTGCTGGTGGTCCTG | 1 (severe disease; patient died at 13 months) | 21-bp deletion in exon 18.16 | 16 |
| c.1250_1256delGAGCCAAinsTGTGAGTGTTGTGTGTG | 1 | Out-of-frame insertion–deletion in exon 20.13 | 13 |
| c.1266+1G>C | 1 | Misplicing of exon 20.20 | 20 |
| c.1266+1delG | 1 | Skipping of exon 20.15 | 15 |
| c.1279_1296delATTGCTGGTGCTCCTGGC | 1 | 18-bp deletion in exon 21.16 | 16 |
| c.1366G>C, p.Gly456Arg | 1 (patient's father is somatic mosaic and has milder disease) (severe disease; patient died at day 1) (p.Gly456Ala is associated with SEDC)27 | Affects the first nucleotide of exon 22 and predicted to alter its splice acceptor site.34 | 9 |
| c.1375G>C, p.Gly459Arg | 1 (severe disease; patient died at day 2) (c.1376G>T, p.Gly459Asp is associated with hypochondrogenesis)13 | Predicted to alter a splice enhancer and creates a splice silencer element in exon 22.34 | 38 |
| c.1419+3_1419+6delGAGT | 1 (severe disease; patient died at 3 months) | Misplicing of exon 22.16 | 16 |
| c.1419+5G>A | 1 (c.1419+5G>T is associated with an SEDC phenotype)26 | Skipping of exon 22 leading to a 54-bp deletion.21 | 21 |
| c.1420-2A>G | 1 (patient's father is somatic mosaic and has milder disease) | Alternative splicing of exon 23 leading to an 18-bp deletion.39 | 33, 39 |
| c.1448G>A, p.Gly483Glu | 1 (also associated with SEDC)13 | Affects an amino acid in exon 23. | This study |
| c.1581+1G>A | 1 (mutation not identified in either parent) (severe disease; patient died at 5 months) | Skipping of exon 24 leading to a 54-bp deletion.40 | 40 |
| c.1681-1G>C | 1 (mutation not identified in either parent) | Misplicing of exon 26.8 | 8 |
| c.1734+5G>A | 1 (severe disease; patient died at day 10) | Skipping of exon 26 leading to a 54-bp deletion.17 | 17, 35, 39 |
| Not reported | 1 (case only mentioned as ‘unpublished work') | 18-bp deletion in exon 36.15, 41 | 15, 41 |
| c.3383G>T, p.Gly1128Val | 1 (mutation not identified in either parent) | Predicted to alter a splice enhancer element in exon 48.34 | 8 |
| c.3627_3644delTCCTCCAGGTCCCCCTGG | 1 (mutation not identified in either parent) | 18-bp deletion in exon 51.41 | 41 |
All variants are described according to the Human Genome Variation Society guidelines based on reference sequence NM_001844.4 (COL2A1). SEDC corresponds to spondyloepiphyseal dysplasia congenita (MIM #183900), another COL2A1-related disorder with a significant skeletal phenotype.