Oxford Molecular Genetics Laboratory
Genetics Laboratories, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
www.ouh.nhs.uk/geneticslab
Juvenile Polyposis Syndrome – OMIM 174900,
600993 (SMAD4), 601299 (BMPR1A)
INTRODUCTION
Juvenile polyposis syndrome (JPS) is a hereditary (autosomal dominant) predisposition to juvenile polyps in the
gastrointestinal tract. The majority of the polyps are benign, however approximately 20% of them undergo malignant
transformation and become cancerous. Individuals with JPS are also at an elevated risk of developing pancreatic
tumours. The age of onset and severity of disease is highly variable, but the overall penetrance of disease in mutation
carriers is estimated to be ~90%. Two JPS causative genes have been identified to date; BMPR1A and SMAD4.
Mutations in both genes cause JPS but mutations in SMAD4 are specifically associated with a combination of juvenile
polyposis and hereditary hemorrhagic telangiectasia (HHT).
TESTING AND REFERRALS
Diagnostic:
o Clinically affected patients.
o UK referrals must be made through Clinical Genetics departments.
Presymptomatic/confirmation test for a familial mutation:
o Individuals at risk of inheriting a pathogenic mutation in SMAD4 or BMPR1A.
o Referrals from Clinical Genetics only.
o Requests for presymptomatic testing should either be accompanied by details of the known pathogenic
mutation in the family or discussed with the laboratory in advance.
Prenatal:
o Prenatal testing is not usually requested.
o Prenatal requests would only be accepted from Clinical Genetics and must be discussed with the
laboratory and arranged in advance.
STRATEGY & TECHNICAL INFORMATION
o Mutation screening in diagnostic referrals is undertaken by fluorescent sequencing analysis of exons 3-13
of BMPR1A and exons 3-13 of SMAD4 (including exon/intron boundaries).
o Dosage analysis by multiplex ligation-dependant probe amplification (MLPA) analysis for large scale
rearrangements of BMPR1A and SMAD4.
o When a pathogenic mutation has been identified in an individual, subsequent testing of family members
(presymptomatic or diagnostic confirmation) involves testing for the familial mutation only.
TARGET REPORTING TIMES
Diagnostic test (2 gene screen):
Presymptomatic/Familial Mutation test:
Prenatal testing (includes maternal contamination check):
40 working days
10 working days
3 working days
CLINICAL SENSITIVITY
JPS: Germline mutations in SMAD4 and BMPR1A account for ~15-20% and ~25-40% of mutations respectively in
patients with a clinical diagnosis of JPS syndrome; (Howe et al. Science 280 (5366): 1086-8, 1998; Howe et al. Nat
Genet 28 (2): 184-7, 2001; Zhou et al.: Am J Hum Genet 69 (4): 704-11, 2001).
JPS/HHT: Germline Mutations in SMAD4 have been detected in approximately 2% of patients with HHT and cause
HHT and juvenile polyposis (JP/HHT) syndrome. Gallione et al, Lancet 2004, 363(9412):852-9.
N.B. Details are correct for the Contact
date of printing
Details: only – last updated 11/06/2015
Duty Scientist
Oxford Regional Molecular Genetics
Laboratory, Churchill Hospital,
Old Road, Headington,
Oxford, OX3 7LE
Tel: 01865 225594
Fax: 01865 225363
oxford.dnalab@nhs.net
http://www.ouh.nhs.uk/geneticslab