An Italian cohort study identifies four new pathologic mutations in the ARSA gene.

Metachromatic leukodystrophy is an autosomal recessive neurodegenerative disorder of the myelin metabolism due to the impaired function of the lysosomal enzyme arylsulfatase A. Three major clinical variants of metachromatic leukodystrophy (MLD) have been described: late infantile, juvenile, and late onset. The infantile form, whose clinical onset is usually before the age of 2 years, is the most frequent.

New Niemann-Pick type C1 gene mutation associated with very severe disease course and marked early cerebellar vermis atrophy.

Niemann-Pick type C is an autosomal recessive lipid storage disease caused by mutations in the NPC1 or NPC2 gene. In childhood-onset Niemann-Pick type C, the usual course is slowly progressive, with normal cerebral magnetic resonance at onset. Here the authors present the case of a patient carrying 2 compound heterozygous NPC1 mutations: the known nonsense mutation (p.

Two new large deletions of the AVPR2 gene causing nephrogenic diabetes insipidus and a review of previously published deletions.

Background: In this paper, we report two new original deletions and present an extended review of the previously characterized AVPR2 gene deletions to better understand the underlying deletion mechanisms.

Methods: The two novel deletions were defined using polymerase chain reaction mapping and junction fragment sequencing. Bioinformatic analysis was performed on both the previously mapped deletions and the novel ones through several web tools.

Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin.

Two missense mutations, R33Q and L167H, of hCASQ2 (human cardiac calsequestrin), a protein segregated to the lumen of the sarcoplasmic reticulum, are linked to the autosomal recessive form of CPVT (catecholaminergic polymorphic ventricular tachycardia). The effects of these mutations on the conformational, stability and Ca(2+) sensitivity properties of hCASQ2, were investigated. Recombinant WT (wild-type) and mutant CASQ2s were purified to homogeneity and characterized by spectroscopic (CD and fluorescence) and biochemical (size-exclusion chromatography and limited proteolysis) methods at 500 and 100 mM KCl, with or without Ca(2+) at a physiological intraluminal concentration of 1 mM; Ca(2+)-induced polymerization properties were studied by turbidimetry.