COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 15, INCLUDED
CRAC1 COLORECTAL CANCER, SUSCEPTIBILITY TO, 4, INCLUDED
COLORECTAL ADENOMA AND CARCINOMA 1
CRCS4, INCLUDED
HMPS1
CHROMOSOME 15q13-q14 DUPLICATION SYNDROME, 40-KB
The hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas (CRC).
- Genetic Heterogeneity of Hereditary Mixed Polyposis
HMPS2 (610069) is caused by mutation in the BMPR1A ... The hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas (CRC). - Genetic Heterogeneity of Hereditary Mixed Polyposis HMPS2 (610069) is caused by mutation in the BMPR1A gene (601299) on chromosome 10q23.
Thomas et al. (1996) noted that HMPS patients may also have an increased propensity to develop inflammatory and metaplastic polyps. The authors stated that in a large HMPS family identified at St. Mark's Hospital, London, HMPS appeared to ... Thomas et al. (1996) noted that HMPS patients may also have an increased propensity to develop inflammatory and metaplastic polyps. The authors stated that in a large HMPS family identified at St. Mark's Hospital, London, HMPS appeared to be inherited as an autosomal dominant. Most older individuals presented with colorectal carcinoma; younger individuals, most of whom had undergone screening by colonoscopy, tended to present with benign colonic lesions, often the characteristic polyp of the hereditary mixed polyposis syndrome. Linkage analysis data did not support linkage to the APC locus (611731) on chromosome 5 or to any of the loci for hereditary nonpolyposis colorectal cancer known at that time. Tomlinson et al. (1999) described an Ashkenazi Jewish family with a dominantly inherited predisposition to colorectal adenomas and carcinomas in which no evidence of linkage was found to previously identified colorectal susceptibility loci.
Using a custom oligonucleotide array, Jaeger et al. (2012) detected a heterozygous single-copy duplication of approximately 40 kb centered on chromosome 15:30.77 Mb (UCSC Genome Browser) in 2 affected individuals from an Ashkenazi Jewish family with HMPS that ... Using a custom oligonucleotide array, Jaeger et al. (2012) detected a heterozygous single-copy duplication of approximately 40 kb centered on chromosome 15:30.77 Mb (UCSC Genome Browser) in 2 affected individuals from an Ashkenazi Jewish family with HMPS that was not present in 3 unaffected relatives. Testing of 40 affected and 50 unaffected family members from 6 Ashkenazi Jewish families with HMPS, previously studied by Thomas et al. (1996), Whitelaw et al. (1997), Tomlinson et al. (1999), and Jaeger et al. (2003), revealed perfect concordance between presence of a duplication-specific 190-bp amplification product and affected status. The 190-bp product was not found in 188 unselected Ashkenazi controls. Screening of 718 familial colorectal cancer (CRC) cases and 935 controls from the Colorectal Tumour Gene Identification (CORGI) study identified 1 additional case with the duplication, which was not detected in any of the controls; on further investigation, the family of the duplication-positive case was found be of Ashkenazi descent and to have a phenotype of multiple polyps and CRC, consistent with HMPS. The duplication extended from intron 2 of the SCG5 gene to a site just upstream of the GREM1 (603054) CpG island, and functional analysis demonstrated that whereas only normal SCG5 mRNA species was found with no difference in expression relative to controls, the duplication was associated with increased and ectopic GREM1 expression.