FTDP-17

In this figure is reported the location of mutations on exons (E9 to E12), on repeats (R) or inter-repeat (IR), provoking an increase of isoforms with exon 10 (+), or a loss of function (-), with a significant decrease of tau binding to tubulin dimers.

Clinical and neuropathological phenotypes are very different according to the mutations, as well as the biochemical signatures. Furthermore, for a given mutation, there is an important heterogenity of the clinical phenotype, inside the same family.

Explanation for tau biochemical signatures, from type I to type IV, click here

Mutation	Localisation	Splice E10	MT<->tau	Phenotype	Bioch. Signature	Remark
R5H	E1	?	?	Late Alzheimer	Doublet PSP
K257T	E9, R1	=	-	Pick	Doublet Pick	Pick-like region
1260V	E9, R1	?	?	?	?
L266V	E9, R1	=		Pick like
G272V	E9, R1	=	-	FTDP-17, Pick-like	Triplet Alzh.
N279K	E10, IR1-2	+	=	PSP	Doublet PSP	4R impact
DK280	E10, IR1-2	-	-	FTDP-17	?
L284L	E10, IR1-2	+	=	Alzheimer	Doublet PSP	Note the PSP phenotype for
N296N	E10, R2	+	=	CBD	Doublet PSP?	all E10 or I10 mutations
DN296	E10, R2	+	-	PSP	?
N296H	E10, R2	+	-	FTDP-17	?
P301L	E10, R2	=	-	PSP/CBD	Doublet PSP
P301S	E10, R2	=	-	PSP/CBD	Doublet PSP
S305N	E10, IR2-3	+	+	CBD	Doublet PSP
S305S	E10, IR2-3	+	=	PSP	Doublet PSP
3	I10	+	=	FTDP-17	Doublet PSP	abnormal splicing region
12	I10	+	=	FTDP-17	Doublet PSP	(mutation in the intron of E10)
13	I10	+	=	?	Doublet PSP
14	I10	+	=	PSP	Doublet PSP
16	I10	+	=	PSP, CBD	Doublet PSP
33	I10	?	?	?	?
S320Y	E11	=	-	Pick	Doublet Pick
V337M	E12, IR3-4	=	-	FTDP-17	Triplet Alzh.
E342V	E12, IR3-4	+?	?	FTDP-17	?
K369I	E12 R4	=	-	FTDP-17/Pick	Triplet Alzh.
G389R	E13	=	-	Pick	Doublet Pick
R406W	E13	=	-	PSP	Triplet Alzh.