Paper alert! We report the first inhibitors for nucleoside kinases NME1-4 and for the nucleotide-binding protein HINT1. On top, we provide probes for MBLAC2, an off-target of every second (!) hydroxamic acid-based HDAC inhibitor! https://t.co/uuRCO78xFz 👇🧵

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent muscle contraction, impaired relaxation and myokymias. Methods: Herein, we describe two brothers in whom biallelic HINT1 variants were identified following a multidisciplinary approach. Results: The younger brother came to our attention for clinical evaluation of moderate intellectual disability, language developmental delay, and some behavioral issues. His elder brother presented mild intellectual disability, hyperactivity, tiptoe walking, and gait ataxia. At first evaluation, motor impairment with frequent falls, pes cavus, and distal hyposthenia with reduced osteotendinous reflexes were found in both. Grip myotonic phenomenon was also noted. Blood tests revealed mildly elevated creatine kinase, and neurophysiology investigations revealed predominantly axonal polyneuropathy. Muscle MRI highlighted fibro-adipose infiltration, prevalent in the lower limbs. Gene panel testing detected a heterozygous HINT1 variant (c.355C>T/p.(Arg119Trp)) on the paternal allele. A further in-depth analysis using Integrative Genomics Viewer and Optical Genome Mapping led us to identify an additional variant in HINT1 represented by a complex rearrangement located in the region 5′UTR-exon 1-intron 1, not previously described. Conclusions: This complex rearrangement could have been overlooked if the clinical picture had not been evaluated as a whole (from a clinical, neurophysiological, and neuroimaging point of view). Neuropsychiatric manifestations (intellectual disability, hyperactivity, etc.) are part of the picture of HINT1-related neuromyotonia.

We have an exciting week ahead of us at lowave, with new music and new artists coming your way- so keep an eye on our socials and follow us on Spotify to be the first to catch the two new releases 👀 Hint1: ⛏️ Hint2: ⚞•⚟ #lowave #newmusic https://t.co/pGXBxOuxrh

@DrNick4126: 1/4 Long overdue – it’s time to rediscover three of the most important Public Health measures that history has taught us: 1) “The general lesson...is that passive protection against healt...

Metalloenzyme inhibitors often incorporate a hydroxamic acid moiety to bind the bivalent metal ion cofactor within the enzyme’s active site. Recently, inhibitors of Zn2+-dependent histone deacetylases...