GM29742

GM29742 Fibroblast from Skin, Skin

Description:

FRONTOTEMPORAL DEGENERATION
MICROTUBULE-ASSOCIATED PROTEIN TAU; MAPT

Affected:

No

Sex:

Female

Age:

34 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Human Variation

Biopsy Source

Skin

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Skin

Race

White

Subject Type

family with at least 3 members, including 1 proband, not a trio

Family Type

NUCLEAR FAMILIES - ONE AFFECTED

Country of Origin

USA

Family Member

Family History

Relation to Proband

child

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Apparently healthy and at risk for Tau R406W; Tau R406W mutation in the MAPT gene confirmed with PCR; At risk for FTD; Clinically affected mother: GM29739; Clinically unaffected father: GM29740; Clinically unaffected brother: GM29741; At risk brother: GM29743.

Characterizations

PDL at Freeze

5.47

Passage Frozen

Gene

MAPT

Chromosomal Location

17q21.1

Allelic Variant 1

157140.0003; FRONTOTEMPORAL DEMENTIA 1; FTD1

Identified Mutation

c.2392C>T (p.Arg798Trp); In affected members of a family from the United States with autosomal dominant frontotemporal dementia (FTD1; 600274) originally reported by Reed et al. (1997), Hutton et al. (1998) identified a heterozygous arg406-to-trp mutation (R406W) in the MAPT gene. Neuropathologic examination identified tau-positive intraneuronal neurofibrillary tangles similar to those found in Alzheimer disease (see 104300). Saito et al. (2002) reported a patient who presented at age 47 years with psychiatric disturbances, primarily delusions, who developed overt dementia by age 52, and died at age 53. There was rapid progression in the last year of life. His father had had a similar illness. Postmortem examination revealed neuronal loss associated with neurofibrillary tangles and neuropil threads, accentuated in the medial temporal lobe, that were immunoreactive for the tau protein. Molecular analysis revealed an R406W mutation. Rademakers et al. (2003) suggested that the R406W mutation can cause a clinical picture closely resembling Alzheimer disease and quite different from frontotemporal dementia with parkinsonism. They described a 6-generation Belgian family that carried the R406W mutation and had such clinical features, and pointed to reports of 2 other families that carried the R406W mutation and had similar clinical characteristics: 1 from the U.S. Midwest with a Danish ancestor (Reed et al., 1997) and 1 from the Netherlands (van Swieten et al., 1999). Haplotype data ruled against a founder effect for the origin of the mutation in western Europe. Rademakers et al. (2003) stated that their report illustrated the phenotypic heterogeneity of MAPT mutations and reemphasized that MAPT should be considered a candidate gene for clinical Alzheimer disease families in which mutations in known Alzheimer disease genes have been excluded.