ORPHA: 157794; DO: 0111686;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q23.2 | Polyposis syndrome, hereditary mixed, 2 | 610069 | 3 | BMPR1A | 601299 |
A number sign (#) is used with this entry because of evidence that hereditary mixed polyposis syndrome-2 (HMPS2) is caused by heterozygous mutation in the BMPR1A (601299) gene on chromosome 10q23.
Hereditary mixed polyposis syndrome-2 (HMPS2) is characterized by colonic polyps of mixed hyperplastic, adenomatous, and occasional juvenile types. Polyposis eventually progresses to colorectal cancer (Cao et al., 2006).
For a discussion of genetic heterogeneity of HMPS, see HMPS1 (601228).
Cao et al. (2006) described two 3-generation Singapore Chinese families with hereditary mixed polyposis (HMPS), noting that the 15 affected members had colonic polyps very similar to those of the HMPS1 family 'SM96' described by Thomas et al. (1996), with polyps showing hyperplastic, adenomatous, or juvenile-type morphology. Juvenile-type polyps were documented in only 4 individuals and were atypical, associated with hyperplastic changes. One-third of patients were documented to have polyps with mixed juvenile and hyperplastic or mixed hyperplastic and adenomatous components on different visits. The mean age of diagnosis in these families was 32.4 years. More than half of the patients had polyps throughout the large bowel; 3 individuals from each family eventually developed colorectal cancer.
In two 3-generation Singapore Chinese families with hereditary mixed polyposis, Cao et al. (2006) excluded linkage to chromosome 15q. A genomewide linkage search on 15 family members from 'family 1' identified a 7-cM putative linkage interval on chromosome 10q23. Haplotype analysis of all 32 members from both families confirmed the linkage, with a maximum multipoint lod score of 4.6 (p less than 0.001); the 10q23.1-10q23.31 haplotypes segregated with disease in both families.
The transmission pattern of HMPS in both families reported by Cao et al. (2006) was consistent with autosomal dominant inheritance.
In affected members of a 3-generation Singapore Chinese family (family 2) with hereditary mixed polyposis, Cao et al. (2006) identified heterozygosity for an 11-bp deletion in the BMPR1A gene (601299.0009). The deletion was not found in unaffected family members. In 2 affected members of 'family 1,' direct sequencing of all exons and flanking sequences of candidate genes BMPR1A, PTEN (601728), MINPP1 (605391), and PCDH21 (609502) revealed no detectable mutations.
Cao, X., Eu, K. W., Kumarasinghe, M. P., Li, H. H., Loi, C., Cheah, P. Y. 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. 43: e13, 2006. Note: Electronic Article. [PubMed: 16525031] [Full Text: https://doi.org/10.1136/jmg.2005.034827]
Thomas, H. J. W., Whitelaw, S. C., Cottrell, S. E., Murday, V. A., Tomlinson, I. P. M., Markie, D., Jones, T., Bishop, D. T., Hodgson, S. V., Sheer, D., Northover, J. M. A., Talbot, I. C., Solomon, E., Bodmer, W. F. Genetic mapping of the hereditary mixed polyposis syndrome to chromosome 6q. Am. J. Hum. Genet. 58: 770-776, 1996. [PubMed: 8644741]