TY - JOUR

T1 - Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort

AU - Lindquist, S G

AU - Schwartz, M

AU - Batbayli, M

AU - Waldemar, G

AU - Nielsen, Jørgen Erik

N1 - Keywords: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cohort Studies; Dementia; Denmark; European Continental Ancestry Group; Family; Female; Genetic Testing; Humans; Male; Middle Aged; Mutation; Phenotype; Referral and Consultation

PY - 2009

Y1 - 2009

N2 - Autosomal dominantly transmitted Alzheimer's disease (AD) and frontotemporal dementia (FTD) are genetically heterogeneous disorders. To date, three genes have been identified in which mutations cause early-onset autosomal dominant inherited AD: APP, PSEN1, and PSEN2. Mutations in two genes on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1, one PSEN2, one APP, one MAPT, and two PGRN) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified.

AB - Autosomal dominantly transmitted Alzheimer's disease (AD) and frontotemporal dementia (FTD) are genetically heterogeneous disorders. To date, three genes have been identified in which mutations cause early-onset autosomal dominant inherited AD: APP, PSEN1, and PSEN2. Mutations in two genes on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1, one PSEN2, one APP, one MAPT, and two PGRN) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified.

U2 - 10.1111/j.1399-0004.2009.01191.x

DO - 10.1111/j.1399-0004.2009.01191.x

M3 - Journal article

C2 - 19659892

VL - 76

SP - 205

EP - 209

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 2

ER -