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%
1.

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

2.

See Molecular Genetics for information on allelic variants.

3.

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

4.

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].

5.

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

6.

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.

7.

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.

8.

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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