Access : Clinical Utility Gene Card for: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014 : European Journal of Human Genetics

Access : Clinical Utility Gene Card for: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014 : European Journal of Human Genetics

Clinical Utility Gene Card Update

European Journal of Human Genetics , (24 September 2014) | doi:10.1038/ejhg.2014.193

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  • Stefan Aretz
  • Hans FA Vasen
  • Sylviane Olschwang

Clinical Utility Gene Card for: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014

Stefan Aretz, Hans FA Vasen and Sylviane Olschwang

Abstract

Update to: European Journal of Human Genetics (2011) 19,doi:10.1038/ejhg.2011.7; published online 2 February 2011Familial adenomatous polyposis (FAP), adenomatous polyposis coli (APC), familial polyposis coli (FPC), attenuated adenomatous polyposis coli (AAPC); phenotypic variants: Gardner syndrome, Turcot syndrome.175100.APC (5q22).611731.

Reference sequences for variant description: LRG_130; NG_008481.4; NM_000038.5; NC_000005.10.

Mutation detection rate: 80–93% in classical FAP.^{1, 2}

De novo events: 10–40%.^{1, 3, 4}

Broad spectrum of point mutations, >90% are truncating (nonsense, del/ins, splice sites).²

Mutational hot spots: c.3927_3931delAAAGA;p.(Glu1309Aspfs*4) (11%), c.3183_3187delACAAA; p.(Gln1062*) (7%), c.637C>T;p.(Arg213*) (3%), c.3202_3205delTCAA;p.(Ser1068Glyfs*57) (2%).

The vast majority of mutations is located in the 5' half of the gene, mutations 3' to codon 1700 are rare (1%).

Genomic rearrangements: large deletions <10–15% in classical FAP; large duplications are very rare.^{5, 6}

In APC/MUTYH mutation-negative families, deep intronic mutations not covered by routine methods have been identified in up to 8% of unselected and up to 30% of familial cases.⁷

Post-zygotic mosaicism in 10–15% of de novo events.⁸

For the mutational spectrum, see locus-specific databases: http://databases.lovd.nl/shared/genes/APC; www.umd.be/APC/, and www.hgmd.cf.ac.uk/ac/. Novel mutations are still being reported.

For variants with no functional effect (‘polymorphisms’), see NCBI accession number NM_000038.5 (www.ncbi.nlm.nih.gov/nuccore/NM_000038.5).