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Table 1 Distribution of CDKL5 mutations within our study group

From: There is variability in the attainment of developmental milestones in the CDKL5 disorder

Mutation group Nucleotide change (cDNA) Protein change Exon/intron Individuals (gender) Reported mutation Reported individual
No functional protein c.-253-?_-163 + ?del p.(0) 1 2 (F) Yes Yes [4]
No functional protein c.-253-?_-163 + ?del p.(0?) 1 1 (F) Yes Yes [4]
No functional protein c.-253-?_99 + ?del p.(0) 1–3 1 (F) Yes Yes [4]
No functional protein c.64 + 2 T > C p.(0) 2 1 (F) Yes No
No functional protein c.64 + 1G > A p.(0) 2 1 (F) Yes Yes [4]
No functional protein c.-162-?_99 + ?del p.(0) 2–3 1 (F) Yes Yes [4]
No functional protein c.-162-?_99 + ? p.(0) 2–3 1 (F) No No
No functional protein c.-253-?_*1085del p.(0) 1–21+ 1 (F) No No
No functional protein c.-253-?_*1085del p.(0) 1–21 3(F) No No
No functional protein c.-253-?_*1085del p.(0) 1–21+ 1 (F) No No
No functional protein c.-253-?_*1085del p.(0) 1–21+ 1 (F) Yes Yes [4]
No functional protein c.-253-?_*1085del p.(0) 1–21+ 1 (F) No No
No functional protein c.65-?_99 + ?del p.(Ala23Asnfs*3) 3 2 (F and M) Yes Yes [4]
No functional protein c.99 + 5G > A p.Ala23Asnfs*3 3 1 (F) Yes Yes [2, 4]
No functional protein c.100-?_*1085del p.(?) 4–21+ 1 (F) No No
No functional protein c.146-1G > A p.(Asn50Tyrfs*15) 5 1 (M) No No
No functional protein c.146-6 T > G p.(Glu49Valfs*2) 5 1 (F) No No
No functional protein c.146-?_282 + ?del p.(Asn50Tyrfs*15) 5 1 (F) Yes Yes [4]
No functional protein c.163_166delGAAA p.Glu55Argfs*20 5 1 (F) Yes No
No functional protein c.175C > T p.Arg59* 5 5 (4 and 1 M) Yes Yes [4, 18, 19]
No functional protein c.183delT p.Met63Cysfs*13 5 2 (F, twins) Yes Yes [4]
No functional protein c.220G > T p.Glu74* 5 1 (F) No No
No functional protein c.282 + 3_282 + 6delAAGT p.(Asn50Tyrfs*15) 5 2 (F) Yes Yes [4]
No functional protein c.283-3_290del p.(Asn95Ilefs*2) 5 2 (F, sisters) Yes Yes [2, 4]
No functional protein c.339ins1 p.? 6 1 (F) No No
No functional protein c.351 T > A p.Tyr117* 6 1 (M) No No
No functional protein c.400C > T p.Arg134* 6 2 (F and M) Yes Yes [4, 20]
No functional protein c.456_457delTG p.Cys152* 7 1 (F) No No
No functional protein c.464-2A > G p.Gly155Alafs*43 7 1 (M) Yes No
No functional protein c.506_507delAC p.Thr168Argfs*36 8 1 (F) No No
Missense/in-frame mutation within catalytic domain c.38 T > C p.Phe13Ser 2 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.58G > C p.Gly20Arg 2 1 (F) Yes Yes [4, 8]
Missense/in-frame mutation within catalytic domain c.100-9_100-3delCCCTTGCinsGCAGA p.(Lys33dup) 4 1 (F) No No
Missense/in-frame mutation within catalytic domain c.119C > T p.Ala40Val 4 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.191 T > C p.Leu64Pro 5 1 (M) Yes Yes [4, 21]
Missense/in-frame mutation within catalytic domain c.214_216del p. Ile72del 5 1 (F) No No
Missense/in-frame mutation within catalytic domain c.215 T > C p.Ile72Thr 5 1 (F) Yes No
Missense/in-frame mutation within catalytic domain c.364G > A p.Ala122Thr 6 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.377G > A p.Cys126Tyr 6 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.395 T > G p.Val132Gly 6 1 (F) No No
Missense/in-frame mutation within catalytic domain c.404A > G p.(Asp135_Phe154del) 7 1 (M) No No
Missense/in-frame mutation within catalytic domain c.404-3C > A p.(Asp135_Phe154del) 7 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.428 T > A p. Ile143Asn 7 1 (F) No No
Missense/in-frame mutation within catalytic domain c.458A > T p. Asp153Val 7 1 (F) No No
Missense/in-frame mutation within catalytic domain c.463 + 1G > A p.Asp135_Phe154del 7 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.473G > C p.Arg158Pro 8 1 (M) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.514G > A p.Val172Ile 8 1 (M) No No
Missense/in-frame mutation within catalytic domain c.526 T > C p.Trp176Arg 8 1 (F) No No
Missense/in-frame mutation within catalytic domain c.532C > T p.Arg178Trp 8 2 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.536C > T p. Ser179Phe 8 1 (F) No No
Missense/in-frame mutation within catalytic domain c.577G > C p.Asp193His 9 1 (F) No No
Missense/in-frame mutation within catalytic domain c.587C > T p.Ser196Leu 9 5 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.595 T > C p.Cys199Arg 9 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.620G > A p.Gly207Glu 9 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.656A > C p.Gln219Pro 9 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.680 T > C p.Leu227Pro 9 1 (F) Yes Yes [4]
Missense/in-frame mutation within catalytic domain c.872G > A p.Cys291Tyr 11 1 (F) Yes No
Truncation occurring between aa 172 and 781 c.670C > T p.Gln224* 9 1 (M) No No
Truncation occurring between aa 172 and 781 c.556_557delGC p.Ala186Serfs*19 9 1 (M) No No
Truncation occurring between aa 172 and 781 c.745-?_977 + ?del p.(Phe249Lysfs*16) 10–11 1 (F) No No
Truncation occurring between aa 172 and 781 c.801_802delAT p.Asn267Lysfs*5 11 1 (F) No No
Truncation occurring between aa 172 and 781 c.857dupA p.Tyr286* 11 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.859_868del10 p.Leu287Serfs*3 11 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.978-?_2980 + ?del p.? 12+ 1 (F) No No
Truncation occurring between aa 172 and 781 c.1039C > T p.Gln347* 12 1 (F) Yes No
Truncation occurring between aa 172 and 781 c.1371dupA p.Leu458Thrfs*5 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1375C > T p.Gln459* 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1446delC p.Tyr482* 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1470_1471delGG p.Ala491Thrfs*3 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1499ins4 p.? 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1547_1554del8 p.Tyr516Phefs*2 12 1 (F) No No
Truncation occurring between aa 172 and 781 c.1581del p.Pro527fs 12 1 (F) No No
Truncation occurring between aa 172 and 781 c.1648C > T p.Arg550* 12 4 (F) Yes Yes (1 child [4])
Truncation occurring between aa 172 and 781 c.1671dupA p.Arg558Thrfs*9 12 1 (F) Yes No
Truncation occurring between aa 172 and 781 c.1675C > T p.Arg559* 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1782 T > G p.Tyr594* 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.1791delC p.Tyr598Thrfs*18 12 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.2038A > T p.Lys680* 13 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.2047-1G > A p.Gly683Valfs*101 13 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.2047-2A > G p.Gly683Cysfs*66 13 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.2072_2073delCT p.Ser691* 14 1 (F) Yes Yes [4]
Truncation occurring between aa 172 and 781 c.2258_2259delAA p.Gln753Profs*10 15 1 (F) No No
Truncation occurring between aa 172 and 781 c.2376 + 5G > A p.(Lys760Tyrfs*10) 16 1 (F) Yes Yes [4]
Late truncation after aa 781 c.2374dupA p.Thr792Asnfs*9 16 1 (F) Yes Yes [4]
Late truncation after aa 781 c.2377-8 T > A p.(Val793Leufs*2) 16 1 (F) No No
Late truncation after aa 781 c.2413C > T p.Gln805* 17 1 (M) No No
Late truncation after aa 781 c.2420_2430del p.Ser807Cysfs*2 17 1 (M) No No
Late truncation after aa 781 c.2504delC p.Pro835Hisfs*2 17 1 (F) Yes Yes [4]
Late truncation after aa 781 c.2477-?_2713 + ?del p.(Ser833Thrfs*22) 17 2 (F) No No
Late truncation after aa 781 c.2564C > G p.Ser855* 18 2 (F) Yes Yes [4]
Late truncation after aa 781 c.2572delC p.Arg858Alafs*5 18 1 (F) Yes Yes [4]
Late truncation after aa 781 c.2635_2636delCT p.Leu879Glufs*30 18 2 (F) Yes Yes [4]
Late truncation after aa 781 c.2711delC p.Pro904Glnfs*23 18 1 (F) Yes Yes [4]
Mutations not grouped
  c.1612A > G p.Thr538Ala 1 1 (M) No No
  c.2684C > T p.Pro895Leu 18 1 (F) No No
  c.65-?_1944 + ?dup p.(?) 3–12 1 (M) No No
  c.146-?_463 + ?dup p.(?) 5–7 1 (F) No No
  (Position uncertain) p.(?) 1–3 1 (M) Yes Yes [4]
  c.745-2A > G p.(Phe249_Lys275del) 10 1 (F) Yes Yes [4]
  c.825 + 1G > A p.(Phe249_Lys275del) 10 1 (F) Yes Yes [4]
  c.825 + 1G > T p.(Phe249_Lys275del) 10 1 (F) Yes No
  c.1030_1031insGAC p.Lys344delinsArgGln 12 1 (F) Yes Yes [4]
  c.2276 + 1G > A p.(Val718_Trp759delinsGly) 15 1 (F) Yes Yes [4]
  1. CDKL5 numbering based on GenBank reference sequences NG_008475.1 and NM_003159.2, with the first A in the start codon numbered +1. Protein names in brackets indicate inferred changes based on in silico analyses, including splicing predictions by SpliceSiteFinder-like (accessed through Alamut Visual v2.3.4), MaxEntScan [22], NNSPLICE by the Berkeley Drosophila Genome Project [23], GeneSplicer [24] and Human Splicing Finder [25].