Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

Autor: Maurizio Genuardi, Robert Blatter, Benjamin Tschupp, Hans F. A. Vasen, Karl Heinimann, Fiona Lalloo, Gabriela Moeslein, D. Gareth Evans, Robert Hüneburg, Frederik J. Hes, Laura Renkonen-Sinisalo, Inge Bernstein, Stefan Aretz, Chrystelle Colas, Isabel Spier, Andrew Latchford, Nicoletta Resta, Heikki Järvinen, Dora Varvara
Přispěvatelé: HUS Abdominal Center, II kirurgian klinikka, Department of Surgery, University of Helsinki, Helsinki University Hospital Area, Clinical sciences, Medical Genetics, University Hospital Basel [Basel], University of Basel (Unibas), University Hospital Bonn, Aalborg University [Denmark] (AAU), Unité fonctionnelle d'Oncogénétique et Angiogénétique Moléculaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Institut Curie [Paris], University of Manchester [Manchester], Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università cattolica del Sacro Cuore [Roma] (Unicatt), Leiden University Medical Center (LUMC), Universität Witten Herdecke, University of Bari Aldo Moro (UNIBA)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
polyposis
030105 genetics & heredity
PHENOTYPE
Settore MED/03 - GENETICA MEDICA
SMAD4
Surveys and Questionnaires
Genetics(clinical)
Juvenile polyposis syndrome
Telangiectasia
Genetics (clinical)
Smad4 Protein
Intestinal Polyposis
Stomach
1184 Genetics
developmental biology
physiology
genotype–phenotype correlation
syndrome
PREVALENCE
GENOTYPE
3. Good health
juvenile polyposis syndrome
medicine.anatomical_structure
Cohort
medicine.symptom
Adult
medicine.medical_specialty
Anemia
[SDV.CAN]Life Sciences [q-bio]/Cancer
colorectal cancer
genotype-phenotype correlation
Article
hereditary hemorrhagic telangiectasia
03 medical and health sciences
Neoplastic Syndromes
Hereditary
Internal medicine
medicine
Humans
Bone Morphogenetic Protein Receptors
Type I
Germ-Line Mutation
BMPR1A
Retrospective Studies
MUTATIONS
business.industry
Cancer
Retrospective cohort study
medicine.disease
digestive system diseases
DELETIONS
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
3111 Biomedicine
business
Zdroj: Genetics in Medicine
Genetics in Medicine, 22(9), 1524-1532. NATURE PUBLISHING GROUP
Genetics in Medicine, Nature Publishing Group, In press, ⟨10.1038/s41436-020-0826-1⟩
Blatter, R, Tschupp, B, Aretz, S, Bernstein, I, Colas, C, Evans, D G, Genuardi, M, Hes, F J, Hüneburg, R, Järvinen, H, Lalloo, F, Moeslein, G, Renkonen-Sinisalo, L, Resta, N, Spier, I, Varvara, D, Vasen, H, Latchford, A R & Heinimann, K 2020, ' Disease expression in juvenile polyposis syndrome : a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers ', Genetics in Medicine, vol. 22, no. 9, pp. 1524-1532 . https://doi.org/10.1038/s41436-020-0826-1
ISSN: 1530-0366
1098-3600
DOI: 10.1038/s41436-020-0826-1⟩
Popis: International audience; Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.Results: We analyzed questionnaire-based data on 221 JPS patients (126 kindreds) from ten European centers and retrieved literature-based information on 473 patients. Compared with BMPR1A carriers, SMAD4 carriers displayed anemia twice as often (58% vs. 26%), and exclusively showed overlap symptoms with hemorrhagic telangiectasia (32%) and an increased prevalence (39% vs. 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41 years), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).Conclusion: This comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management, and provides the basis for open access variant SMAD4 and BMPR1A databases.
Databáze: OpenAIRE
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