RGD Reference Report - Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot. - Rat Genome Database

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Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot.

Authors: Howe, JR  Shellnut, J  Wagner, B  Ringold, JC  Sayed, MG  Ahmed, AF  Lynch, PM  Amos, CI  Sistonen, P  Aaltonen, LA 
Citation: Howe JR, etal., Am J Hum Genet. 2002 May;70(5):1357-62. Epub 2002 Mar 27.
RGD ID: 1599899
Pubmed: PMID:11920286   (View Abstract at PubMed)
PMCID: PMC447611   (View Article at PubMed Central)
DOI: DOI:10.1086/340258   (Journal Full-text)

Juvenile polyposis (JP) is an autosomal dominant syndrome in which affected patients develop upper- and/or lower-gastrointestinal (GI) polyps. A subset of families with JP have germline mutations in the SMAD4 (MADH4) gene and are at increased risk of GI cancers. To date, six families with JP have been described as having the same SMAD4 deletion (1244-1247delAGAC). The objective of the present study is to determine whether this deletion is a common ancestral mutation or a mutational hotspot. DNA from members of four families with JP, from Iowa, Mississippi, Texas, and Finland, that had this 4-bp deletion was used to genotype 15 simple tandem repeat polymorphism (STRP) markers flanking the SMAD4 gene, including 2 new STRPs within 6.3 and 70.9 kb of the deletion. Haplotypes cosegregating with JP in each family were constructed, and the distances of the closest markers were determined from the draft sequence of the human genome. No common haplotype was observed in these four families with JP. A 14-bp region containing the deletion had four direct repeats and one inverted repeat. Because no common ancestor was suggested by haplotype analysis and the sequence flanking the deletion contains repeats frequently associated with microdeletions, this common SMAD4 deletion in JP most likely represents a mutational hotspot.

Objects referenced in this article
Gene SMAD4 SMAD family member 4 Homo sapiens
Gene Smad4 SMAD family member 4 Mus musculus
Gene Smad4 SMAD family member 4 Rattus norvegicus

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