Cation leak through the ATP1A3 pump causes spasticity and intellectual disability.

ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.

Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.

X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes.

A SCN4A mutation causing paramyotonia congenita.

Paramyotonia congenita (OMIM 168300) is a non-dystrophic myopathy caused by mutations in the SCN4A gene that sometimes can be confused with myotonia congenita. Another disease also caused by mutations in the gene SCN4A is called myotonia aggravated by potassium (OMIM 170500, 613345). It is estimated that more than 20% of patients with suspected myotonia congenita suffer paramyotonia congenita.

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis.

Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD.

Normal HPRT coding region in complete and partial HPRT deficiency.

Lesch-Nyhan syndrome is an X-linked recessive inborn error of metabolism due to a virtually complete lack of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity (OMIM 300322). Partial deficiency of HPRT (OMIM 300323) is characterized by the effects of excess uric acid synthesis and a continuum spectrum of neurological manifestations, without the manifestations of full-blown Lesch-Nyhan syndrome. Both diseases have been associated with mutations in the HPRT gene.

Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency.

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a genetic disease of purine metabolism resulting in uric acid overproduction. Allopurinol, which inhibits the enzyme xanthine oxidase and reduces uric acid synthesis, is widely used for the treatment of gout and uric acid overproduction. The aim of the study was to analyze the long-term efficacy and safety of allopurinol in patients with HPRT deficiency.

Adenosine transport in peripheral blood lymphocytes from Lesch-Nyhan patients.

We postulated that adenosine function could be related to some of the neurological features of Lesch-Nyhan syndrome and therefore characterized adenosine transport in PBLs (peripheral blood lymphocytes) obtained from Lesch-Nyhan patients (PBL(LN)) and from controls (PBL(C)). Adenosine transport was significantly lower in PBL(LN) when compared with that in PBL(C) and a significantly lower number of high affinity sites for [(3)H]nitrobenzylthioinosine binding were quantified per cell ( B (max)) in PBL(LN) when compared with that in PBL(C). After incubation with 25 microM hypoxanthine, adenosine transport was significantly decreased in PBL(LN) with respect to PBL(C).