Table 3. Sex and CDKL5 genetic variants of a cohort of 26 individuals with CDD who underwent neurological and ophthalmological evaluations in the CDKL5 clinic at Boston Children’s Hospital.
Genotype groups are as defined by Helen Leonard and colleagues4.
| Sex | cDNA Variant† | Protein Change | Variant classification# | |
|---|---|---|---|---|
| Genotype group A = no functional protein (truncations before aa 172 and whole gene deletions) | ||||
| 1 | F | Xp22.2p22.13 (16721094–18581822) x1 | Deletion involving exons 1–6 | Pathogenic |
| 2 | F | Xp22.13 (18468786–18666025) x1 | Deletion involving exons 2–21 | Pathogenic |
| 3 | F | c.100-(9_3)delCCCTTGCinsGCAGA | Damage/destroy natural slice acceptor site of intron 3 | Pathogenic |
| 4 | F | c.383delA | p.Lys128Argfs*9 (mosaic) | Pathogenic |
| 5 | F | c.400C>T | p.Arg134* | Pathogenic |
| Genotype group B = Missense variants in the kinase domain | ||||
| 6 | M | c.320T>A | p.Val107Asp | Likely Pathogenic |
| 7 | F | c.470C>T | p.Ala157Val | Likely Pathogenic |
| 8 | F | c.533G>A | p.Arg178Gln | Pathogenic |
| 9 | F | c.620G>A | p.Gly207Glu | Likely Pathogenic |
| 10 | F | c.637G>C | p.Gly213Arg | Likely Pathogenic |
| Genotype group C = Truncations from amino acid 172 to 781 inclusive | ||||
| 11 | F | c.700C>T | p.Gln234* | Pathogenic |
| 12 | F | Xp22.13 (18604167–18604591) x1 | Deletion involving exons 12–14 | Likely Pathogenic |
| 13 | F | c.1412delA | p.Asp471fs*22 | Pathogenic |
| 14 | F | c.1648C>T | p.Arg550* | Pathogenic |
| 15 | F | c.1671dupA | p.Arg558Thrfs*9 | Pathogenic |
| 16 | F | c.1671dupA | p.Arg558Thrfs*9 | Pathogenic |
| 17 | F | c.1782T>G | p.Tyr594* | Pathogenic |
| 18 | F | c.1791delC | p.Tyr598Thrfs*18 | Pathogenic |
| 19 | M | c.1886T>A | p.Leu629* (mosaic) | Pathogenic |
| 20 | F | c.1909delG | p.Ala637Leufs*21 | Pathogenic |
| 21 | M | c.2152G>A | p.Val718Met (mosaic, known splice effect) | Pathogenic |
| 22 | F | c.2326_2327delAA | p.Lys776Alafs*24 | Likely Pathogenic |
| Genotype group D = Truncations after amino acid 781 | ||||
| 23 | F | Xp22.13 (18618238–18626562) x1 | Deletion involving exons 16–17 | Likely Pathogenic |
| 24 | F | Xp22.13 (18635012–18713396) x1 | Deletion involving exons 17–21 | Likely Pathogenic |
| 25 | F | c.2463G>A | p.Trp821* | Pathogenic |
| 26 | M | c.2522dupA | p.Leu842Valfs*68 | Pathogenic |
#
Variant classification was done according to American College of Medical Genetics guidelines and all patients had pathogenic or likely pathogenic variants.8
†
Deletions are listed using Genome Reference Consortium Human Build 38 (hg38) and the minimum genomic coordinates are provided.