Posts By: Nicola Brunetti-Pierri

A novel inborn error of vitamin B12 metabolism

Posted by & filed under Part 14: METALS.

Coelho et al. have identified a new disease that results in failure to release vitamin B12 from lysosomes. Affected patients present with methylmalonic aciduria and hyperhomocysteinemia. This disorder is caused by mutations in ABCD4, a gene that encodes for an ABC transporter, which was previously thought to have peroxisomal localization and function. ABCD4 colocalizes with […]

Cyclocreatine for therapy of creatine transporter deficiency

Posted by & filed under Part 21: MEMBRANE TRANSPORT DISORDERS, Treatment.

The second most common cause of X-linked mental retardation is the deficiency of creatine transporter (encoded by SLC6A8), which leads to speech and language disorders with severe cognitive impairment. This syndrome is caused by cerebral creatine deficiency. Kurosawa et al. have treated the Slc6a8–/y mice with cyclocreatine, a creatine analog which is more susceptible to […]

Cholesterol-enriched diet for treatment of Pelizaeus-Merzbacher disease

Posted by & filed under Part 28: NEUROGENETICS.

A letter recently published in Nature Medicine reports the role of diet enriched in cholesterol for treatment of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy due to increased dosage of the gene encoding the proteolipid protein 1 (PLP1) . The major finding of this study is that cholesterol promotes normal trafficking of PLP and PMD mice […]

Proteostasis modulator for Niemann–Pick type C disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

The paper by Yu et al. reports a strategy for modulating  cellular proteostasis and restore functional activity of NPC1 in primary fibroblasts of patients with Niemann–Pick type C disease. The authors of this paper found that ryanodine receptor (RyR) antagonists increased steady-state NPC1 levels in fibroblasts carrying the p.I1061T mutation, which is degraded by the proteasome. These compounds also […]

Collaboration effort for discovery of genes responsible for Mendelian diseases

Posted by & filed under Exome sequencing.

Exome and whole genome sequencing by next generation sequencing have shown tremendous potential for discovery of genes underlying Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Genomics at Yale University; and the Baylor–Johns Hopkins […]


Posted by & filed under Part 28: NEUROGENETICS.

Campbell and colleagues found through a GWAS a significant association of autism spectrum disorder (ASD) with a SNP located in a gene-poor region of chromosome 5p14.1. They found that individuals who carry this ASD-associated SNP showed increased expression of  moesin pseudogene 1, antisense(MSNP1AS), a noncoding RNA encoded by the moesin pseudogene 1 (MSNP1). MSNP1AS is […]