Adenomatous Polyposis Phenotype in BMPR1A and SMAD4 Variant Carriers.
Journal
Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
received:
25
06
2022
accepted:
10
08
2022
pubmed:
2
9
2022
medline:
3
11
2022
entrez:
1
9
2022
Statut:
epublish
Résumé
Variants in SMAD4 or BMPR1A cause juvenile polyposis syndrome, a rare autosomal dominant condition characterized by multiple gastrointestinal hamartomatous polyps. A phenotype of attenuated adenomatous polyposis without hamartomatous polyps is rare. We describe a retrospective cohort of individuals with SMAD4 or BMPR1A heterozygous germline variants, having ≥10 cumulative colorectal adenomas and/or colorectal cancer without hamartomatous polyps. All individuals had multigene panel and duplication/deletion analysis to exclude other genetic syndromes. The study cohort included 8 individuals. The pathogenic potential of the variants was analyzed. Variants detected included 4 missense variants, 1 nonsense variant, 1 splice site variant, and 2 genomic deletions. Features of pathogenicity were present in most variants, and cosegregation of the variant with polyposis or colorectal cancer was obtained in 7 of the 8 families. Three of 8 individuals had colorectal cancer (age less than 50 years) in addition to the polyposis phenotype. Two individuals had extraintestinal neoplasms (pancreas and ampulla of Vater). The clinical phenotype of SMAD4 and BMPR1A variants may infrequently extend beyond the classical juvenile polyposis syndrome phenotype. Applying multigene panel analysis of hereditary cancer-related genes in individuals with unexplained polyposis can provide syndrome-based clinical surveillance for carriers and their family members.
Identifiants
pubmed: 36049049
doi: 10.14309/ctg.0000000000000527
pii: 01720094-202210000-00004
pmc: PMC9624493
doi:
Substances chimiques
SMAD4 protein, human
0
Smad4 Protein
0
BMPR1A protein, human
EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type I
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00527Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
Références
Burt RW, Bishop DT, Lynch HT, et al. Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. Bull World Health Organ 1990;68:655–65.
Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: A molecular review. Int J Colorectal Dis 2009;24:865–74.
Latchford AR, Neale K, Phillips RK, et al. Juvenile polyposis syndrome: A study of genotype, phenotype, and long-term outcome. Dis Colon Rectum 2012;55:1038–43.
McColl I, Busxey HJ, Veale AM, et al. Juvenile polyposis coli. Proc R Soc Med 1964;57:896–7.
Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015;110:223–62.
Calva-Cerqueira D, Chinnathambi S, Pechman B, et al. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. Clin Genet 2009;75:79–85.
Cheah PY, Wong YH, Chau YP, et al. Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome. Am J Gastroenterol 2009;104:3027–33.
Gao XH, Li J, Zhao ZY, et al. Juvenile polyposis syndrome might be misdiagnosed as familial adenomatous polyposis: A case report and literature review. BMC Gastroenterol 2020;20:167.
Sayed MG, Ahmed AF, Ringold JR, et al. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol 2002;9:901–6.
Aretz S, Stienen D, Uhlhaas S, et al. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet 2007;44:702–9.
Grover S, Kastrinos F, Steyerberg EW, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 2012;308:485–92.
Stanich PP, Pearlman R, Hinton A, et al. Prevalence of germline mutations in polyposis and colorectal cancer-associated genes in patients with multiple colorectal polyps. Clin Gastroenterol Hepatol 2019;17:2008–15.
O'Riordan JM, O'Donoghue D, Green A, et al. Hereditary mixed polyposis syndrome due to a BMPR1A mutation. Colorectal Dis 2010;12:570–3.
Cao X, Eu KW, Kumarasinghe MP, et al. Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet 2006;43:e13.
Haramis AP, Begthel H, van den Born M, et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 2004;303:1684–6.
Rohlin A, Rambech E, Kvist A, et al. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing. Fam Cancer 2017;16:195–203.
Cragun D, Radford C, Dolinsky JS, et al. Panel-based testing for inherited colorectal cancer: A descriptive study of clinical testing performed by a US laboratory. Clin Genet 2014;86:510–20.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular pathology. Genet Med 2015;17:405–24.
Lieberman S, Beeri R, Walsh T, et al. Variable features of juvenile polyposis syndrome with gastric involvement among patients with a large genomic deletion of BMPR1A. Clin Transl Gastroenterol 2019;10:e00054.
Blatter R, Tschupp B, Aretz S, et al. 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. Genet Med 2020;22:1524–32.
Ishida H, Ishibashi K, Iwama T. Malignant tumors associated with juvenile polyposis syndrome in Japan. Surg Today 2018;48:253–63.
Aytac E, Sulu B, Heald B, et al. Genotype-defined cancer risk in juvenile polyposis syndrome. Br J Surg 2015;102:114–8.
Cross W, Kovac M, Mustonen V, et al. The evolutionary landscape of colorectal tumorigenesis. Nat Ecol Evol 2018;2:1661–72.