Analysis of Single Nucleotide Polymorphisms (SNPs) of the small-conductance calcium activated potassium channel (SK3) gene as genetic modifier of the cardiac phenotype in myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is the most frequently inherited neuromuscular disease in adults. It is a multisystemic disorder with major cardiac involvement most commonly represented by first-degree atrioventricular heart block (AVB), followed by different degrees of bundle-branch and intraventricular blocks In search for candidate genes, modifiers of the AVB phenotype in DM1, the expression of the small-conductance calcium activated potassium channel (SK3) gene was analysed in muscle biopsies from DM1 patients. The association between SK3 polymorphisms and the AVB phenotype was then studied analyzing 40 DM1 patients with AVB and 40 age-matched DM1 affected individuals with no ECG abnormalities.

Gene expression analysis in myotonic dystrophy: indications for a common molecular pathogenic pathway in DM1 and DM2.

An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCN1) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs.

Risk prediction for clinical phenotype in myotonic dystrophy type 1: data from 2,650 patients.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. DM1 is caused by expansion of a CTG trinucleotidedaggerrepeat in the gene DMPK. Clinical findings in DM1 span a continuum from mild to severe.

Italian guidelines for molecular analysis in myotonic dystrophies.

Myotonic dystrophies, the most common form of adult muscular dystrophy, comprise at least two forms, clinically and genetically heterogeneous. Myotonic dystrophy type 1 and type 2 are both caused by unstable repetitions in untranslated gene regions: a [CTG]n expansion in the 3' region of the DMPK gene on chromosome 19q13 (DM1) and [CCTG]n tetranucleotide repeat located in the first intron of the ZNF9 gene on chromosome 3q21 (DM2). DM clinical features are caused by a gain of functions RNA mechanism in which the CUG and CCUG repeats alter nuclear functions, including alternative splicing of shared genes.

Use of RNA fluorescence in situ hybridization in the prenatal molecular diagnosis of myotonic dystrophy type I.

Background: Myotonic dystrophy type 1 (DM1; OMIM #160900) is an autosomal-dominant genetic disorder with multisystemic clinical features associated with a CTG expansion in the 3' untranslated region of the DMPK gene on chromosome 19q13.3. A long-PCR protocol to detect the DM1 expansion is rapid, sensitive, and accurate, but interpretative limitations can occur when the expansion size exceeds the PCR amplification range and in cases of somatic mosaicism.

Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2).

Myotonic dystrophy is caused by two different mutations: a (CTG)n expansion in 3' UTR region of the DMPK gene (DM1) and a (CCTG)n expansion in intron 1 of the ZNF9 gene (DM2). The most accredited mechanism for DM pathogenesis is an RNA gain-of-function. Other findings suggest a contributory role of DMPK-insufficiency in DM1.

Characterization of a single nucleotide polymorphism in the ZNF9 gene and analysis of association with myotonic dystrophy type II (DM2) in the Italian population.

Myotonic dystrophy type 2 (DM2) is a dominant inherited disorder clinically similar to myotonic dystrophy type 1 (DM1) with a peculiar pattern of multisystemic phenotypic features. The mutation responsible for DM1 is a CTG repeat in the 3' UTR of the dystrophia myotonica protein kinase gene (DMPK) on chromosome 19q13.3, while DM2 is caused by an unstable CCTG expansion in intron 1 of the zinc finger protein 9 gene (ZNF9) on chromosome 3q21.

A long PCR-based molecular protocol for detecting normal and expanded ZNF9 alleles in myotonic dystrophy type 2.

Myotonic dystrophy type 2 (DM2) lacks the expansion on chromosome 19q13 present in DM1 and is characterized by a mutation on 3q21. It has been shown that the DM2 mutation is a huge [CCTG]n repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. The longest normal allele observed has a approximately 30 CCTG repeat, whereas the range of expansion is extremely variable, starting from 75 up to 11,000 CCTGs.

Exclusion of CARD15/NOD2 as a candidate susceptibility gene to psoriasis in the Italian population.

Psoriasis is a chronic inflammatory skin disorder showing multifactorial inheritance. Linkage studies have mapped disease susceptibility loci to several genomic regions, including the chromosome 16 interval that contains the CARD15/NOD2 gene. CARD15 has been involved in Crohn's Disease (CD) susceptibility and it has been hypothesised that it may also contribute to the pathogenesis of psoriasis.

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families.

Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity. It is caused mainly by a 1.5 Mb duplication in 17p11.