Table 1 |
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Mutations in the presenilin genes |
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PS1 |
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|
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|
Codon |
Location |
Mutation |
Phenotype |
|
|
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|
35 |
Amino-terminal domain |
Arg→Gln |
FAD |
|
79 |
Amino-terminal domain |
Ala→Val |
FAD, onset 64 years |
|
82 |
TM1 |
Val→Leu |
FAD, onset 55 years |
|
94 |
TM1 |
Val→Met |
See [71] |
|
96 |
TM1 |
Val→Phe |
FAD, onset 53 years |
|
105 |
TM1/TM2 loop |
Phe→Leu |
FAD, onset 52 years |
|
113-114 (insert) |
TM1/TM2 loop |
Insert Thr |
FAD, onset 35 years |
|
115 |
TM1/TM2 loop |
Tyr→His |
FAD, onset 37 years |
|
115 |
TM1/TM2 loop |
Tyr→Cys |
FAD, onset 42 years |
|
116 |
TM1/TM2 loop |
Thr→Asn |
FAD, onset 37 years |
|
117 |
TM1/TM2 loop |
Pro_Leu |
AD, onset 28 years |
|
120 |
TM1/TM2 loop |
Glu_Asp |
FAD, onset 48 years |
|
120 |
TM1/TM2 loop |
Glu_Lys |
FAD, onset 37 years |
|
123 |
TM1/TM2 loop |
Glu_Lys |
FAD, onset 56-62 years |
|
135 |
TM2 |
Asn_Asp |
FAD, onset 36 years |
|
139 |
TM2 |
Met_Thr |
FAD, onset 49 years |
|
139 |
TM2 |
Met_Val |
FAD, onset 40 years |
|
139 |
TM2 |
Met_Ile |
AD |
|
139 |
TM2 |
Met_Lys |
FAD, onset 37 years |
|
143 |
TM2 |
Ile_Thr |
FAD, onset 35 years |
|
143 |
TM2 |
Ile_Phe |
FAD, onset 55 years |
|
146 |
TM2 |
Met_Leu |
FAD, onset 45 years |
|
146 |
TM2 |
Met_Val |
FAD, onset 38 years |
|
146 |
TM2 |
Met_Ile |
FAD, onset 40 years |
|
147 |
TM2 |
Thr_Ile |
FAD, onset 42 years |
|
156 + insert |
TM3 interface |
Tyr_ (Phe,Ile,Tyr) |
FAD |
|
163 |
TM3 interface |
His_Arg |
FAD, onset 50 years |
|
163 |
TM3 interface |
His_Tyr |
FAD, onset 47 years |
|
165 |
TM3 |
Trp_Cys |
FAD, onset 42 years |
|
169 |
TM3 |
Ser_Leu |
FAD, onset 31 years |
|
169 |
TM3 |
Ser_Pro |
FAD, onset 35 years |
|
171 |
TM3 |
Leu_Pro |
FAD, onset 40 years |
|
173 |
TM3 |
Leu_Trp |
FAD, onset 27 years |
|
177 |
TM3 |
Phe_Ser |
FAD |
|
178 |
TM3 |
Ser_Pro |
FAD |
|
184 |
TM3 |
Glu_Asp |
FAD |
|
206 |
TM4 |
Gly_Ser |
FAD |
|
209 |
TM4 |
Gly_Val |
FAD, onset 30-48 years |
|
209 |
TM4 |
Gly_Arg |
FAD, onset 49 years |
|
213 |
TM4 interface |
Ile_Thr |
FAD, onset 42-48 years |
|
213 |
TM4 interface |
Ile_Leu |
FAD |
|
219 |
TM4 interface |
Leu_Pro |
FAD |
|
219 |
TM4 interface |
Leu_Phe |
See [71] |
|
222 |
TM5 |
Gln_Arg |
FAD |
|
231 |
TM5 |
Ala_Thr |
FAD, onset 52 years |
|
231 |
TM5 |
Ala_Val |
FAD |
|
233 |
TM5 |
Met_Thr |
FAD, onset 35 years |
|
233 |
TM5 |
Met_Leu |
FAD, onset 46 years |
|
235 |
TM5 |
Leu_Pro |
FAD, onset 32 years |
|
237 |
TM5 |
Phe_Ile |
AD with spastic paraparesis, 31 years |
|
246 |
TM6 |
Ala_Glu |
FAD, onset 55 years |
|
250 |
TM6 |
Leu_Ser |
FAD, onset 53 years |
|
260 |
TM6 |
Ala_Val |
FAD, onset 40 years |
|
261 |
TM6 |
Val_Phe |
FAD |
|
262 |
TM6 |
Leu_Phe |
FAD, onset 50 years |
|
263 |
TM6/TM7 loop |
Cys_Arg |
FAD, onset 47 years |
|
264 |
TM6/TM7 loop |
Pro_Leu |
FAD, onset 45 years |
|
267 |
TM6/TM7 loop |
Pro_Ser |
FAD, onset 35 years |
|
269 |
TM6/TM7 loop |
Arg_Gly |
FAD, onset 47 years |
|
269 |
TM6/TM7 loop |
Arg_His |
FAD, onset 47 years |
|
273 |
TM6/TM7 loop |
Glu_Ala |
FAD, onset 63 years |
|
274 |
TM6/TM7 loop |
Thr_Arg |
FAD |
|
278 |
TM6/TM7 loop |
Arg_Thr |
FAD, onset 37 years |
|
280 |
TM6/TM7 loop |
Glu_Ala |
FAD, onset 47 years |
|
280 |
TM6/TM7 loop |
Glu_Gly |
FAD, onset 42 years |
|
282 |
TM6/TM7 loop |
Leu_Arg |
FAD, onset 43 years |
|
285 |
TM6/TM7 loop |
Ala_Val |
FAD, onset 50 years |
|
286 |
TM6/TM7 loop |
Leu_Val |
FAD, onset 50 years |
|
290 |
TM6/TM7 loop |
Ser>Cys |
FAD, onset 39-50 years |
|
291-319 deletion |
TM6/TM7 loop |
Shortened loop |
FAD |
|
352 (insert) |
TM6/TM7 loop |
Insert Arg |
FAD |
|
354 |
TM6/TM7 loop |
Thr_Ile |
FAD |
|
358 |
TM6/TM7 loop |
Arg_Gln |
FAD |
|
365 |
TM6/TM7 loop |
Ser_Tyr |
FAD |
|
378 |
TM7 |
Gly_Glu |
FAD, onset 35 years |
|
384 |
TM7 |
Gly_Ala |
FAD, onset 35 years |
|
390 |
TM7 |
Ser_Ile |
FAD, onset 39 years |
|
392 |
TM7 |
Leu_Val |
FAD, onset 25-40 years |
|
394 |
TM7 |
Gly_Val |
FAD |
|
405 |
TM7/TM8 loop |
Asn_Ser |
FAD, onset 48 years |
|
409 |
TM8 |
Ala_Thr |
FAD, onset 58 years |
|
410 |
TM8 |
Cys_Tyr |
FAD, onset 48 years |
|
418 |
TM8 |
Leu_Phe |
FAD |
|
424 |
TM8 |
Leu_Arg |
FAD, onset 33 years |
|
426 |
TM8 |
Ala_Pro |
FAD, onset 48-60 years |
|
431 |
Carboxy-terminal domain |
Ala_Glu |
FAD |
|
434 |
Carboxy-terminal domain |
Ala_Cys |
FAD |
|
435 |
Carboxy-terminal domain |
Leu_Phe |
FAD |
|
436 |
Carboxy-terminal domain |
Pro_Ser |
FAD, onset 48-60 years |
|
436 |
Carboxy-terminal domain |
Pro_Gln |
FAD, onset 48-60 years |
|
439 |
Carboxy-terminal domain |
Ile_Val |
FAD |
|
PS2 |
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|
Codon |
Location |
Mutation |
Phenotype |
|
|
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|
62 |
N-term |
Arg_His |
AD, onset 62 years |
|
122 |
TM1/TM2 loop |
Thr_Pro |
FAD, onset 46 years |
|
141 |
TM2 |
Asn_Ile |
FAD, onset 50-65 years |
|
148 |
TM2 |
Val_Ile |
AD, Onset 71 years |
|
239 |
TM5 |
Met_Val |
FAD, onset variable 45- |
|
84 yrs |
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|
239 |
TM5 |
Met_Ile |
FAD, onset 58 years |
|
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Compiled from [2,70,71]. Abbreviations: AD, Alzheimer's disease; FAD,familial Alzheimer's disease; TM, transmembrane segment; TM1/TM2 loop, the loop between transmembrane segments 1 and 2. The age of onset of disease is given if it is known. |
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Tandon and Fraser Genome Biology 2002 3:reviews3014.1 doi:10.1186/gb-2002-3-11-reviews3014 |
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