Mutation type*1 |
Mutation position |
Length of affected nucleotides |
Nucleotide sequence after mutation |
Mutation name |
Case # |
Consequence |
Disease |
Onset Age |
Gender |
Lymphoproliferation |
Autoimmunity |
Excess CD4-/CD8-Tcells |
Apoptosis Impairment/Ab:Fas |
Reference |
Compound Heterozygote |
N |
219 |
1 |
A |
C57X |
1 |
TGC-TGA at ntd 219 -> Cys-Stop at codon 57 |
Autoimmune lymphoproliferative syndrome |
3y |
Female |
lymphadenopathy, hepatosplenomegaly |
Guillain-Barre syndrome |
CD3+CD4-8-TCRa/b+=15 |
21 |
Sneller,M.C. et al. Blood 89,1341(1997) |
- |
M |
244 |
1 |
C |
C66R |
1 |
TGC-CGC at ntd 244 -> Cys-Arg at codon 66 |
Canale-Smith syndrome |
2.5y |
Female |
lymphadenopathy, hepatosplenomegaly |
Hemolytic anemia, membranous nephropathy |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
M |
361 |
1 |
T |
R105W |
1 |
CGG-TGG at ntd 361 -> Arg-Trp at codon 105 |
Autoimmune lymphoproliferative syndrome |
1m |
Male |
splenomegaly, lymphadenopathy |
hypergammaglobulinemia |
CD4-8-TCRa/b+=41 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 1 |
M |
361 |
1 |
T |
R105W |
1 |
CGG-TGG at ntd 361 -> Arg-Trp at codon 105 |
Autoimmune lymphoproliferative syndrome |
1y6m |
Male |
splenomegaly, lymphadenopathy |
Autoimmune hemolytic anemia, thrombocytopenia |
CD4-8-TCRa/b+=45 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 2 |
M |
361 |
1 |
T |
R105W |
1 |
CGG-TGG at ntd 361 -> Arg-Trp at codon 105 |
Autoimmune lymphoproliferative syndrome |
1y |
Male |
splenomegaly, lymphadenopathy |
ND*2 |
CD4-8-TCRa/b+=37 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 3 |
M |
695 |
1 |
G |
Y216C |
1 |
TAT-TGT at ntd 695 -> Tyr-Cys at codon 216 |
Autoimmune lymphoproliferative syndrome |
1m |
Male |
splenomegaly, lymphadenopathy |
hypergammaglobulinemia |
CD4-8-TCRa/b+=41 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 1 |
M |
695 |
1 |
G |
Y216C |
1 |
TAT-TGT at ntd 695 -> Tyr-Cys at codon 216 |
Autoimmune lymphoproliferative syndrome |
1y6m |
Male |
splenomegaly, lymphadenopathy |
Autoimmune hemolytic anemia, thrombocytopenia |
CD4-8-TCRa/b+=45 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 2 |
M |
695 |
1 |
G |
Y216C |
1 |
TAT-TGT at ntd 695 -> Tyr-Cys at codon 216 |
Autoimmune lymphoproliferative syndrome |
1y |
Male |
splenomegaly, lymphadenopathy |
ND |
CD4-8-TCRa/b+=37 |
7 |
Bettinardi,A. et al. Blood 89,902(1997) |
patient 3 |
M |
722 |
1 |
A |
T225K |
1 |
ACA-AAA at ntd 722 -> Thr-Lys at codon 225 |
Autoimmune lymphoproliferative syndrome |
5y |
ND |
lymphadenopathy, hepatosplenomegaly |
ND |
CD3+CD4-8-TCRa/b+=8_18 |
0 |
Jackson,C.E. et al. Am.J.Hum.Genet. 64,1002(1999) |
- |
M |
721 |
1 |
C |
T225P |
1 |
ACA-CCA at ntd 721 -> Thr-Pro at codon 225 |
Autoimmune lymphoproliferative syndrome |
5y |
Male |
adenopathy, spleen enlargement |
hemolytic anemia, urticarial rash, neutropenia, thrombocytopenia |
CD3+CD4-8-=15 |
10 |
Fisher,G.H. et al. Cell 81,935(1995) |
- |
M |
749 |
1 |
A |
R234Q |
1 |
CGA-CAA at ntd 749 -> Arg-Gln at codon 234 |
Autoimmune lymphoproliferative syndrome |
2y |
ND |
lymphadenopathy, hepatosplenomegaly |
ND |
CD3+CD4-8-TCRa/b+=2 |
0 |
Jackson,C.E. et al. Am.J.Hum.Genet. 64,1002(1999) |
- |
M |
749 |
1 |
C |
R234P |
1 |
CGA-CCA at ntd 749 -> Arg-Pro at codon 234 |
Canale-Smith syndrome |
Neonate |
Female |
ND |
Severe Autoimmune hemolytic anemia, rashes(s), neutropenia, thrombocytopenia |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
N |
748 |
1 |
T |
R234X |
1 |
CGA-TGA at ntd 748 -> Arg-Stop at codon 234 |
Autoimmune lymphoproliferative syndrome |
4m |
Male |
splenomegaly, lymphadenopathy |
hemolytic anemia, neutropenia, thrombocytopenia, hypergammaglobulinemia |
CD3+CD4-8-=>20 |
11 |
Drappa,J. et al. N.Engl.J.Med. 335,1643(1996) |
- |
M |
770 |
1 |
A |
A241D |
1 |
GCC-GAC at ntd 770 -> Ala-Asp at codon 241 |
Autoimmune lymphoproliferative syndrome |
4m |
Female |
lymphadenopathy, hepatosplenomegaly |
hemolytic anemia |
CD3+CD4-8-TCRa/b+=13 |
21 |
Sneller,M.C. et al. Blood 89,1341(1997) |
- |
M |
779 |
1 |
G |
D244G |
1 |
GAT-GGT at ntd 779 -> Asp-Gly at codon 244 |
Canale-Smith syndrome |
Neonate |
Male |
lymphadenopathy, hepatosplenomegaly |
Autoimmune hemolytic anemia, thrombocytopenia |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
M |
779 |
1 |
T |
D244V |
1 |
GAT-GTT at ntd 779 -> Asp-Val at codon 244 |
Autoimmune lymphoproliferative syndrome |
Neonate |
Male |
hepatosplenomegaly, adenopathy |
hemolytic anemia |
CD4-8-TCRa/b+=2.1 |
1 |
Infante,A.J. et al. J.Pediatr. 133,629(1998) |
- |
M |
778 |
1 |
T |
D244Y |
1 |
GAT-TAT at ntd 778 -> Asp-Tyr at codon 244 |
Autoimmune lymphoproliferative syndrome |
7m |
Male |
massive lymphadenopathy |
Autoimmune hemolytic anemia, thrombocytopenia |
CD3+CD4-8-=>20 |
13 |
Drappa,J. et al. N.Engl.J.Med. 335,1643(1996) |
- |
M |
809 |
1 |
T |
T254I |
1 |
ACA-ATA at ntd 809 -> Thr-Ile at codon 254 |
Canale-Smith syndrome |
Neonate |
Female |
lymphopenia, lymphoadenopathy |
neutropenia, Autoimmune hemolytic anemia, recurrent painful oral ulceration, premature ovarian failure(s) |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
N |
817 |
1 |
T |
Q257X |
1 |
CAG-TAG at ntd 817 -> Gln-Stop at codon 257 |
Autoimmune lymphoproliferative syndrome |
2m |
Male |
adenopathy, spleen enlargement |
hemolytic anemia, urticarial rash, neutropenia, thrombocytopenia |
CD3+CD4-8-=16 |
NoDATA |
Fisher,G.H. et al. Cell 81,935(1995) |
- |
N |
826 |
1 |
T |
Q260X |
1 |
CAA-TAA at ntd 826 -> Gln-Stop at codon 260 |
Autoimmune lymphoproliferative syndrome |
11m |
ND |
lymphadenopathy, splenomegaly |
hemolytic anemia |
CD3+CD4-8-TCRa/b+=6_9 |
0 |
Jackson,C.E. et al. Am.J.Hum.Genet. 64,1002(1999) |
- |
M |
929 |
1 |
G |
I294S |
1 |
ATT-AGT at ntd 929 -> Ile-Ser at codon 294 |
Autoimmune lymphoproliferative syndrome |
4m |
Female |
lymphadenopathy, hepatosplenomegaly |
hemolytic anemia, neutropenia |
CD3+CD4-8-TCRa/b+=11 |
18 |
Sneller,M.C. et al. Blood 89,1341(1997) |
- |
S |
334+2 |
0 |
T |
334+1insT |
1 |
1-bp ins T at ntd 334+1 -> splice doner site change after codon 95; abberant splicing |
Autoimmune lymphoproliferative syndrome |
18m |
Female |
adenopathy, spleen enlargement |
hemolytic anemia, urticarial rash, thrombocytopenia, glomerulitis |
CD3+CD4-8-=40 |
40 |
Fisher,G.H. et al. Cell 81,935(1995) |
- |
FI |
165 |
0 |
GGCCAAT |
165ins7 |
1 |
7-bp ins GGCCAAT at ntd 165 -> frameshift at codon 42 |
Canale-Smith syndrome |
2y |
Male |
lymphadenopathy, hepatosplenomegaly |
urticarial rashes, Autoimmune hemolytic anemia, thrombocytopenia |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
FI |
692 |
0 |
T |
692insT |
1 |
1-bp ins T at ntd 692 -> frameshift at codon 215 |
Autoimmune lymphoproliferative syndrome |
15y? |
Female |
lymphadenopathy |
hypergammaglobulinemia, thrombocytopenia |
CD3+CD4-8-=>20 |
3 |
Drappa,J. et al. N.Engl.J.Med. 335,1643(1996) |
- |
FD |
46 |
2 |
|
46delGC |
1 |
2-bp del GC at ntd 46 -> frameshift at codon -2 |
Canale-Smith syndrome |
4y |
Male |
lymphadenopathy |
Guillain-Barre syndrome, Autoimmune hemolytic anemia, thrombocytopenia |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
FD |
235 |
1 |
|
235delG |
1 |
1-bp del G at ntd 235 -> frameshift at codon 62 |
Autoimmune lymphoproliferative syndrome |
6m |
Male |
adenopathy, spleen enlargement |
urticarial rash, neutropenia, thrombocytopenia |
CD3+CD4-8-=30 |
45 |
Fisher,G.H. et al. Cell 81,935(1995) |
- |
FD |
809 |
2 |
|
809delCA |
1 |
2-bp del CA at ntd 809 -> frameshift at codon 253 |
Autoimmune lymphoproliferative syndrome |
5y |
Female |
hepatosplenomegaly |
neutropenia, thrombocytopenia, hypergammaglobulinemia |
CD3+CD4-8-=41 |
20 |
Rieux-Laucat,F. et al. SCIENCE 268,1347(1995) |
- |
FD |
809 |
2 |
|
809delCA |
1 |
2-bp del CA at ntd 809 -> frameshift at codon 253 |
Autoimmune lymphoproliferative syndrome |
Neonate |
Male |
hepatosplenomegaly |
hemolytic anemia, autoimmune thrombocytopenia, hypergammaglobulinemia |
CD3+CD4-8-=38 |
20 |
Rieux-Laucat,F. et al. SCIENCE 268,1347(1995) |
- |
FD |
880 |
1 |
|
880delT |
1 |
1-bp del T at ntd 880 -> frameshift at codon 277 |
Autoimmune lymphoproliferative syndrome |
1y |
ND |
lymphadenopathy, splenomegaly |
hemolytic anemia, glomerulonephritis, immune-mediated thrombocytopenia purpura, autoimmune neutropenia |
CD3+CD4-8-TCRa/b+=7_19 |
5 |
Jackson,C.E. et al. Am.J.Hum.Genet. 64,1002(1999) |
- |
S |
569-2 |
1 |
C |
549-2A->C |
1 |
ntd 562-2 A-C -> splice acceptor site change after codon 173; abbebant splicing |
Autoimmune lymphoproliferative syndrome |
2y |
Male |
adenopathy, spleen enlargement |
urticarial rash, neutropenia |
CD3+CD4-8-=18 |
45 |
Fisher,G.H. et al. Cell 81,935(1995) |
- |
S |
651+2 |
1 |
A |
651+2T->A |
1 |
ntd 651+2 T-A -> splice doner site change after codon 201; frameshift, termination at position 209 |
Canale-Smith syndrome |
Neonate |
Male |
lymphadenopathy, hepatosplenomegaly |
Hemolytic anemia, urticarial rash, thrombocytopenia |
increase |
<40% of ctrl |
Vaishnaw,A.K. et al. J.Clin.Invest. 103,355(1999) |
- |
LD |
916 |
290 |
|
916del290 |
1 |
Large Deletion in Exon 9 |
Autoimmune lymphoproliferative syndrome |
Neonate |
Female |
hepatosplenomegaly |
autoimmune thrombocytopenia, hypergammaglobulinemia |
CD3+CD4-8-=70 |
NotDetect |
Rieux-Laucat,F. et al. SCIENCE 268,1347(1995) |
- |