Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS.

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data.

Validation of IRF5 as multiple sclerosis risk gene: putative role in interferon beta therapy and human herpes virus-6 infection.

In recent reports, IRF5 polymorphisms showed significant association with multiple sclerosis (MS) susceptibility in three studied populations and Irf5-deficient mice exhibited an increased susceptibility to viral infection, linked to a significant decrease in the induction of serum type I interferon (IFN). In the present study, we evaluated the association of two IRF5 polymorphisms with MS predisposition and we also addressed whether these polymorphisms were associated with active replication of human herpes virus-6 (HHV-6) observed in a subgroup of MS patients, and/or with response to IFN-β therapy. A total of 1494 MS patients and 1506 ethnically matched controls were genotyped for rs4728142 and rs3807306 with TaqMan pre-designed assays.

Validation of the CD6 and TNFRSF1A loci as risk factors for multiple sclerosis in Spain.

A recent meta-analysis of genome-wide association screens coupled to a replication exercise in a combined US/UK collection led to the identification of 4 single nucleotide polymorphisms (SNPs) in three gene loci, i.e. TNFRSF1A, CD6 and IRF8, as novel risk factors for multiple sclerosis with genome-wide level of significance.

Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2.

Episodic ataxia type 2 is a rare autosomal dominant disease characterized by recurrent attacks of vertigo and cerebellar ataxia. The disease was caused by mutations in the CACNA1A gene, on chromosome 19p. We perform a mutational screening in a group of 43 unrelated patients.

Progression from idiopathic portal hypertension to incomplete septal cirrhosis with liver failure requiring liver transplantation.

We report the case of a 30-year-old male patient suffering from what was initially thought to be end-stage cryptogenic cirrhosis with portal hypertension and liver failure, who underwent liver transplantation. Histological examination of the surgical specimen showed incomplete septal cirrhosis. At the age of 17 this patient had presented pancytopenia and splenomegaly, which were treated by splenectomy.