Table 1.

Summary of Molecular Genetic Testing Used in Early-Onset Familial Alzheimer Disease

Gene 1Proportion of EOFAD Attributed to Mutations in This GeneTest MethodMutations Detected 2Mutation Detection Frequency by Gene and Test Method 3
PSEN130%-70% 4 Targeted mutation analysis4555-bp deletion of exon 9 (Finnish founder mutation5100% for the targeted mutation
Sequence analysis 6Sequence variants~98%
Deletion/duplication analysis 7Partial- and whole-gene deletions, including exon 9 Finnish founder deletion100% for deletions, which are rare
APP10%-15%Sequence analysis 6 / mutation scanning 8 of exons 16 and 17Sequence variants in exons 16 and 1799%
Deletion/duplication analysis 7Partial- and whole-gene duplications100% for the targeted duplication
PSEN2<5%Sequence analysis 6Sequence variants~100%

See Table A. Genes and Databases for chromosome locus and protein name.


See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a mutation that is present in the indicated gene


The highest yield for identification of a mutation in PSEN1 is for persons with early-onset (age <60 years) AD who have another affected family member (especially a parent) with early-onset AD [Rogaeva et al 2001, Lleó et al 2002, Janssen et al 2003, Tedde et al 2003].


Finnish population, this mutation is rarely observed in other populations.


Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


Sequence analysis and mutation scanning can have similar mutation detection frequencies; however, mutation detection frequencies for mutation scanning may vary considerably among laboratories depending on the specific protocol used.

From: Early-Onset Familial Alzheimer Disease

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