Biomedical subjects

Cliff J Meldrum

Publications and source records attributed to Cliff J Meldrum.

4 recordsLinked to original sources

PubMed2005

Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations.

The MYH gene has recently been shown to be associated with a recessive form of colorectal adenomatous polyposis. Two common mutations in the MYH gene have been identified that lend themselves to rapid screening. We have examined a series of 302 individuals comprising 120 control subjects, 120 patients diagnosed with adenomatous polyposis but without germline mutations in the APC gene and 62 patients diagnosed with familial adenomatous polyposis all harbouring confirmed causative APC germline mutations. The results reveal that MYH accounts for 16 percent of polyposis patients without germline mutations in the APC gene and that it does not appear to be a modifier gene in FAP patients diagnosed with APC germline mutations.

Adenomatous Polyposis Coli↗

PubMed2004

Phenotype-genotype correlations in a series of wolfram syndrome families.

OBJECTIVE: Wolfram syndrome is an extremely rare autosomal-recessive disorder that predisposes the development of type 1 diabetes in association with progressive optic atrophy. The genetic basis of this disease has been shown to be due to mutations in the WFS1 gene. The WFS1 gene encodes a novel transmembrane protein called wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic beta-cells and neurons. Genotype-phenotype correlations in this syndrome are becoming apparent and may help in explaining some of the variable characteristics observed in this disease. RESEARCH DESIGN AND METHODS: In this report, we have studied 13 patients with Wolfram syndrome from nine families to further define the relationship between mutation site and type with specific disease characteristics. RESULTS: A severe phenotype was seen in patients with mutations in exon 4 and with a large deletion encompassing most of exon 8. In total, nine novel mutations were identified as well as three new silent polymorphisms. CONCLUSIONS: Similar to all other mutation reports, most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified outside this region in exon 4.

Adolescent↗

PubMed2002

BRCA2 mutations in a population-based series of patients with ocular melanoma.

We studied the BRCA2 gene for germline mutations in 71 of 99 patients (72%) with ocular melanoma who were diagnosed consecutively in Australia in 1997 and 1998. Patients considered for our study fulfilled one of the following critiera: (i) were 50 years of age or less at diagnosis; (ii) had bilateral disease (2 patients); (iii) reported a family history of ocular melanoma (4 patients). Mutation detection was performed using the protein truncation test and denaturing high-performance liquid chromatography with primers designed to include intron-exon boundaries. Six DNA changes were found of which 2 were exonic, in exons 14 (A>C in nucleotide 7244 leading to His>Arg) and 27 (base pair substitution in nucleotide 9976 leading to a stop codon). One exonic change has been reported previously. None of the intronic mutations were deemed to affect splicing efficiency. Neither exonic mutation was in a person with bilateral ocular melanoma or a family history of cutaneous melanoma. We estimated the prevalence of possible loss of function changes in BRCA2 in patients with ocular melanoma at 3% (95% CI 0-10%). This figure was similar to previous estimates of 2.8% and 2% in nonrepresentative samples of patients with ocular melanoma and 2.1% in a representative sample of young women with breast cancer.

Adolescent↗

PubMed2002

Direct integrin alphavbeta6-ERK binding: implications for tumour growth.

Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In alphavbeta6-expressing cells ERK2 is bound only to the beta6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by beta6-bound ERK. Deletion of the ERK2 binding site on the beta6 cytoplasmic domain inhibits tumour growth and leads to an association between ERK and the beta5 subunit. The physical interaction between integrin alphavbeta6 and ERK2 defines a novel paradigm of integrin-mediated signalling and provides a therapeutic target for cancer treatment.

Amino Acid Sequence↗