Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis

M G Sayed; A F Ahmed; J R Ringold; M E Anderson; J L Bair; F A Mitros; H T Lynch; S T Tinley; G M Petersen; F M Giardiello; B Vogelstein; J R Howe

doi:10.1007/BF02557528

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Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis

Journal article

Peer reviewed

Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis

M G Sayed, A F Ahmed, J R Ringold, M E Anderson, J L Bair, F A Mitros, H T Lynch, S T Tinley, G M Petersen, F M Giardiello, …

Annals of surgical oncology, Vol.9(9), pp.901-906

11/2002

DOI: 10.1007/BF02557528

PMID: 12417513

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Abstract

Juvenile polyposis (JP) is an inherited condition predisposing to upper gastrointestinal (UGI) polyps and colorectal cancer. Two genes are known to predispose to JP, SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A). The object of this study was to determine the differences in phenotype of patients with SMAD4 or BMPR1A mutations (MUT+) compared with those without (MUT-). DNA was extracted from 54 JP probands and used for polymerase chain reaction of all exons of SMAD4 and BMPR1A. Products were then sequenced and analyzed for mutations. Medical record data were used to create a JP database, and statistical analysis was performed using Fisher's exact and unpaired t-tests. Nine of 54 patients had germline SMAD4 mutations, 13 had BMPR1A mutations, and 32 had neither. There were no significant differences between SMAD4+ and BMPR1A+ cases in terms of clinical factors examined, except for a family history of UGI involvement (P <.01). There was a higher prevalence of familial cases in MUT+ patients (P =.09), >10 lower gastrointestinal polyps (P =.06), and frequency of family history of gastrointestinal cancer compared with MUT- patients (P =.01). Patients with germline SMAD4 or BMPR1A mutations have a more prominent JP phenotype than those without, and SMAD4 mutations predispose to UGI polyposis.

Phenotype

Genetic Predisposition to Disease

Humans

Protein-Serine-Threonine Kinases - genetics

Smad4 Protein

DNA-Binding Proteins - genetics

Receptors, Growth Factor - genetics

Intestinal Polyps - genetics

DNA Mutational Analysis

Adolescent

Trans-Activators - genetics

Bone Morphogenetic Protein Receptors, Type I

Germ-Line Mutation

Child

Genes, Tumor Suppressor

Details

Title: Subtitle: Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis
Creators: M G Sayed - University of Iowa College of Medicine, Iowa City, Iowa, USA
A F Ahmed - University of Iowa
J R Ringold - University of Iowa
M E Anderson - University of Iowa
J L Bair - University of Iowa
F A Mitros - University of Iowa
H T Lynch - Creighton University
S T Tinley - Creighton University
G M Petersen - Mayo Clinic
F M Giardiello - Johns Hopkins University
B Vogelstein - Johns Hopkins University
J R Howe - University of Iowa
Resource Type: Journal article
Publication Details: Annals of surgical oncology, Vol.9(9), pp.901-906
Publisher: United States
DOI: 10.1007/BF02557528
PMID: 12417513
ISSN: 1068-9265
eISSN: 1534-4681
Language: English
Date published: 11/2002
Academic Unit: Pathology; Surgery
Record Identifier: 9984051741502771

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