Article

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

Journal of Medical Genetics (Impact Factor: 5.64). 04/2006; 43(3):e13. DOI: 10.1136/jmg.2005.034827
Source: PubMed

ABSTRACT Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC.
We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1-10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family.
Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis-carcinoma sequence.

Download full-text

Full-text

Available from: Pehyean Cheah, Jul 27, 2015
0 Followers
 · 
96 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer is one of most common digestive malignant tumours; both the incidence and mortality are on the top list. Studies show that nearly a third of the colorectal cancer was caused by hereditary colorectal tumours. Hereditary colorectal tumours mainly include two categories: hereditary nonpolyposis colorectal cancer and hereditary colorectal polyposis; and hereditary colorectal polyposis can also be divided into two types: adenomatous polyposis syndrome and hamartoma polyposis syndrome; including a serial of diseases, such as familial adenomatous polyposis, Peutz-Jeghers syndrome, familial juvenile polyposis coli, PTEN hamartoma tumor syndrome, hereditary mixed polyposis syndrome, et al. Hereditary colorectal tumours is one of the hotspot of clinical oncology for its special genetic basis and clinicopathologic features. In order to deepen people's understanding and improve clinicians' diagnostic ability of hereditary colorectal tumors, the research progress and agreement of hereditary colorectal tumors are
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are a variety of applications in industrial automation where ultrasound can be used to detect the presence of (count) transparent or light sensitive objects (or liquid), such as ampoules or photographic films. Dusty or smoking surroundings are also places where ultrasound is used for presence detection instead of light. In applications where detection must take place in a small enclosure, such as counting drops of medicine in a drip, a miniaturized sensor is desirable. In such applications a fully-integrated ultrasound microsystem in a IC-compatible technology has an advantage in both size and cost. This fully-integrated IC, is configurable either as a transmitter or as a receiver, to bind two micromachined ultrasound membranes into a general purpose barrier-detecting microsystem. Miniaturized microsystems today are usually designed to take full advantage of the rapid progress of both the integrated sensor and integrated circuit technologies. A trend in such systems is to integrate sensors, in this case the ultrasound transducer, using the same technology as the integrated circuits. The advantage of realizing sensors and circuits on the same chip is to tap the strong manufacturing base of the IC technologies perfected in low-cost mass production. The ultrasound transducer with which this circuit forms a microsystem is a silicon membrane that can be micromachined out of a BiCMOS technology using one simple post-processing step. The complete system is in 3 μm BiCMOS and has a maximum range of 10 cm
    Solid-State Circuits Conference, 1997. Digest of Technical Papers. 43rd ISSCC., 1997 IEEE International; 03/1997
  • [Show abstract] [Hide abstract]
    ABSTRACT: Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations. We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques. APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations. We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance.
    The American Journal of Gastroenterology 12/2006; 101(12):2810-7. DOI:10.1111/j.1572-0241.2006.00842.x · 9.21 Impact Factor
Show more