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Background. Little information is available on a long-term follow-up in Bartter syndrome type I and II. Methods. Clinical presentation, treatment and long-term follow-up (5.0-21, median 11years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. Results. Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90mL/min/1.73m2 in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. Conclusions. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10years. Gallstones might represent a new complication of antenatal Bartter syndrome

A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases.We noticed that, using a panel of 184 Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I80, Bw4T80, Bw6 and HLA-C1 or -C2 supratype.

Hexanucleotide repeat expansions in the C9orf72 gene is the prevalent genetic cause of ALS, causing neurodegeneration through two gain-of-function mechanisms due to the accumulation of RNA foci and dipeptide-repeat proteins, and a loss-of-function mechanism due to C9orf72 protein reduction. The loss-of-function has never been examined in the peripheral compartment of neuromuscular system, precociously affected by ALS. In this work we observed that C9orf72 is expressed by Schwann cells and skeletal muscle in mice and the constitutive ablation of C9orf72 leads to mild muscle denervation, alterations of autophagy, increased immune cell infiltration and inflammation in muscle and peripheral nerve, typical features of ALS. Moreover, demyelination, activation of Schwann cells in a repair mode and autoimmunity were found in peripheral nerves of C9orf72-/- mice. Evidence demonstrates that the loss-of-function synergizes with other toxic stimuli to induce neurodegeneration. Moreover, C9orf72 mutation often occurs in combination with other ALS or FTD-linked genes, suggesting oligogenicity of ALS. Therefore, to verify whether the C9orf72 loss-of-function could act as ALS modulator, we investigated the effect of C9orf72 constitutive ablation in SOD1G93A mice, the best characterized model of ALS. We found that the C9orf72 loss-of-function anticipated the onset of symptoms exacerbating denervation, autophagy impairment and inflammation in muscle, and enhancing axonal transport disruption in SOD1G93A mice. Conversely, increased anti-inflammatory gliosis in the spinal cord and extended survival were detected in SOD1G93A C9orf72-/- mice. For the first time, in this work we demonstrated that C9orf72 is expressed in the peripheral compartment of neuromuscular system where it is pivotal in maintaining the homeostasis. Despite the C9orf72 ablation had detrim

Hexanucleotide repeat expansions in the C9orf72 gene is the prevalent genetic cause of ALS, causing neurodegeneration through two gain-of-function mechanisms due to the accumulation of RNA foci and dipeptide-repeat proteins, and a loss-of-function mechanism due to C9orf72 protein reduction. The loss-of-function has never been examined in the peripheral compartment of neuromuscular system, precociously affected by ALS. In this work we observed that C9orf72 is expressed by Schwann cells and skeletal muscle in mice and the constitutive ablation of C9orf72 leads to mild muscle denervation, alterations of autophagy, increased immune cell infiltration and inflammation in muscle and peripheral nerve, typical features of ALS. Moreover, demyelination, activation of Schwann cells in a repair mode and autoimmunity were found in peripheral nerves of C9orf72-/- mice. Evidence demonstrates that the loss-of-function synergizes with other toxic stimuli to induce neurodegeneration. Moreover, C9orf72 mutation often occurs in combination with other ALS or FTD-linked genes, suggesting oligogenicity of ALS. Therefore, to verify whether the C9orf72 loss-of-function could act as ALS modulator, we investigated the effect of C9orf72 constitutive ablation in SOD1G93A mice, the best characterized model of ALS. We found that the C9orf72 loss-of-function anticipated the onset of symptoms exacerbating denervation, autophagy impairment and inflammation in muscle, and enhancing axonal transport disruption in SOD1G93A mice. Conversely, increased anti-inflammatory gliosis in the spinal cord and extended survival were detected in SOD1G93A C9orf72-/- mice. For the first time, in this work we demonstrated that C9orf72 is expressed in the peripheral compartment of neuromuscular system where it is pivotal in maintaining the homeostasis. Despite the C9orf72 ablation had detrim

Background. Little information is available on a long-term follow-up in Bartter syndrome type I and II. Methods. Clinical presentation, treatment and long-term follow-up (5.0-21, median 11years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. Results. Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90mL/min/1.73m2 in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. Conclusions. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10years. Gallstones might represent a new complication of antenatal Bartter syndrome