MBNL1 gene variants as modifiers of disease severity in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic autosomal dominant disorder characterized by a highly variable phenotype and caused by an unstable CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Longer CTG repeat expansions often correlate with an anticipated age at onset and CTG repeat number may account for 45-60 % of the variance in disease severity. In order to search for candidate genes that could act as modifiers of disease severity, we studied the association between Muscleblind-like protein-1 (MBNL1) gene polymorphisms and the DM1 phenotype.

Evaluation of predictive models in daily practice for the identification of patients with Lynch syndrome.

The optimal strategy for identifying patients with Lynch syndrome among patients with newly diagnosed colorectal cancer (CRC) is still debated. Several predictive models (e.g.

Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening.

Background: The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing remains a critical issue. The Bethesda guidelines were developed to preselect patients for microsatellite instability (MSI) testing before germline mutation screening. These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed.

Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases.

We investigated the possible role of chromosome 10q losses in colorectal cancer metastasis by carrying out an allelic imbalance study on a series of microsatellite instability-negative (MSI-) primary tumours (n=32) and metastases (n=36) from 49 patients. Our results demonstrate that 10q allelic losses are associated with a significant proportion (25%) of MSI- colorectal tumours, but are not involved in the metastatic process. PTEN and BMPR1A, two genes located in the common deleted region, were screened for mutations in samples with loss of heterozygosity.

Giardia lamblia infection in a patient with myotonic dystrophy.

Myotonic dystrophy is an autosomal dominant muscle disorder characterized by muscle wasting and weakness and a number of other systemic abnormalities. Some patients have hypo-IgG that is asymptomatic in most of them. We report the case of a 42-year-old woman with myotonic dystrophy and hypo-IgG who experienced asthenia and weight loss secondary to Giardia lamblia bowel infection.

No evidence of somatic FGFR3 mutation in various types of carcinoma.

Germline specific point mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal dysplasia and craniosynostosis syndromes. Mutations identical to the germinal activating mutations found in severe skeletal dysplasias have been identified in certain types of cancer: at low frequency in multiple myeloma and cervix carcinoma and at high frequency in bladder carcinoma. We analysed, by SSCP and sequencing, the prevalence of FGFR3 mutations in 116 primary tumours of various types (upper aerodigestive tract, oesophagus, stomach, lung and skin).

Transgenic mice carrying large human genomic sequences with expanded CTG repeat mimic closely the DM CTG repeat intergenerational and somatic instability.

Myotonic dystrophy (DM) is caused by a CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. A very high level of instability is observed through successive generations and the size of the repeat is generally correlated with the severity of the disease and with age at onset. Furthermore, tissues from DM patients exhibit somatic mosaicism that increases with age.

Somatic instability of the CTG repeat in mice transgenic for the myotonic dystrophy region is age dependent but not correlated to the relative intertissue transcription levels and proliferative capacities.

A (CTG)nexpansion in the 3'-untranslated region (UTR) of the DM protein kinase gene ( DMPK ) is responsible for causing myotonic dystrophy (DM). Major instability, with very large expansions between generations and high levels of somatic mosaicism, is observed in patients. There is a good correlation between repeat size (at least in leucocytes), clinical severity and age of onset.

Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice.

Myotonic dystrophy (DM) is associated with the expansion of a (CTG)n trinucleotide repeat in the 3' untranslated region (UTR) of the DM protein kinase gene (DMPK). The (CTG)n repeat is polymorphic and varies in size between 5 and 37 repeats in unaffected individuals whereas in affected patients there are between 50 and 4,000 CTGs. The size of the (CTG)n repeat, which increases through generations, generally correlates with clinical severity and age of onset.

Intriguing association between disease associated unstable trinucleotide repeat and CpG island.

Expansion of (C+G)-rich trinucleotide repeats has been shown to be associated with several autosomal or X-linked genetic diseases and/or fragile sites. By analysing the sequences available in the databases, we found, in a significant proportion of triplet associated genes or fragile sites (11/12), a CpG island close to the trinucleotide repeat. This association led us to assume that flanking regions and chromatin structure near the triplets might play a role in repeat instability.

Specific tau variants in the brains of patients with myotonic dystrophy.

The mutation causing myotonic dystrophy (DM) is an unstable CTG trinucleotide repeat in a gene encoding for a protein with putative serine-threonine kinase activity. Several studies have reported the appearance of abnormally frequent neurofibrillary tangles (NFTs) in the cortex of patients with DM. Using immunologic probes against normal and pathologic hyperphosphorylated tau proteins, the basic components of NFTs, we performed a biochemical and immunohistochemical study of the brains of two DM cases.

French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion.

The molecular basis of myotonic dystrophy (DM) has been characterised. All DM mutations characterised to date appear as an unstable elongation of a fragment containing a tandem repeat of a CTG motif, which can be visualised in both EcoRI and BamHI digests. It has been shown that the fragment is polymorphic in the normal population.

Myotonic dystrophy: over-expression or/and under-expression? A critical review on a controversial point.

Myotonic dystrophy (DM) results from the amplification of an unstable (CTG)n sequence in the 3' untranslated region of the myotonin-protein kinase (MT-PK) gene. The expression of the enlarged allele in DM patients with a number of repeats below or beyond 200, was analysed by three different groups. Two groups showed a decreased or absent expression of mutant alleles in DM adults, in congenitally affected infants (CDM) and in an affected fetus.

Myotonic dystrophy: absence of CTG enlarged transcript in congenital forms, and low expression of the normal allele.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease. The mutation has been identified as an unstable trinucleotide CTG repeat in a sequence encoding a putative cAMP-dependent protein kinase. The CTG repeat varies in length between affected siblings, and generally increases through generations in parallel with increasing severity of the disease.

Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism.

Myotonic dystrophy (DM) is a progressive neuromuscular disorder which results from elongations of an unstable (CTG)n repeat, located in the 3' untranslated region of the DM gene. A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease. However, the clinical status of patients cannot be unambiguously ascertained solely on the basis of the number of CTG repeats.