Re-recognition of BMPR1A-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome
Zi-Ye Zhao1, Ye Lei2, Zhao-Ming Wang1
1Department of Colorectal Surgery and Hereditary Colorectal Cancer Registry, Changhai Hospital, Shanghai, P. R. China.
Insights
Juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, caused by BMPR1A mutations, represent a single spectrum of disease. Phenotypes vary, including colorectal cancer, not just typical juvenile polyps.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- Bone morphogenetic protein receptor type 1A (BMPR1A) mutations are linked to juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2.
- These syndromes share overlapping clinical features, prompting investigation into their relationship.
Purpose of the Study:
- To determine if juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2 are distinct entities or subtypes of a single syndrome.
- To characterize the phenotypic spectrum associated with BMPR1A germline mutations.
Main Methods:
- Sequencing of the BMPR1A gene in 186 patients with polyposis and colorectal cancer.
- Evaluation of clinicopathological features and phenotypes in mutation carriers and their relatives.
Main Results:
- BMPR1A germline mutations were identified in six probands and three relatives.
- Mutations included frameshift, nonsense, splice-site, and missense types, with two novel mutations found.
- Phenotypes ranged from mixed polyposis to isolated colorectal cancer; typical juvenile polyps were not consistently present.
Conclusions:
- BMPR1A-related diseases manifest as a spectrum, from mixed polyposis to colorectal cancer, with variable presentation of juvenile polyps.
- These findings support classifying BMPR1A-associated conditions as a single syndrome.
- Genetic testing for BMPR1A mutations is recommended for identifying individuals with this spectrum of disease.
Background:
Bone morphogenetic protein receptor type 1A (BMPR1A) is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes.
Methods:
We sequenced the BMPR1A gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with BMPR1A mutations.
Results:
BMPR1A germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps.
Conclusions:
Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of BMPR1A-mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying BMPR1A-related syndromes.
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