PRO-148 / Sophia Laboratories - LARVOL DELTA

Exome Sequencing Uncovers Genetic Drivers of Multiple Sclerosis in a Multiplex Family. (PubMed, Genes (Basel)) - "Three missense variants in genes involved in inflammation, autoimmunity, and demyelinization were identified as the most promising candidates: c.443 C>T, p.Pro148Leu in the RTN4 gene, c.1678 T>G, p.Phe560Val in the JAK2 gene, and c.3449 A>G, p.Tyr1150Cys in the DUOX2 gene... We identified novel candidate genes for MS in a multiplex family, providing evidence for an oligogenic model of disease susceptibility. Further replication and functional studies are required to validate these preliminary results."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • DUOX2 • JAK2 • RTN4

Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1. (PubMed, Commun Biol) - "Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it...This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range."

Journal • Ebola Virus Disease • Infectious Disease

KIF22 Mutation with Spondyloepimetaphyseal Dysplasia with Joint Laxity, Leptodactylic Type 2 (SEMDJL2) (ESPE 2024) - "A genetic analysis revealed a heterozygousvariant inthe KIF22gene, specifically a c.443C>T (p.Pro148Leu) variant... In the context of severe short stature, it may be helpful to consider SEMD leptodactylic type in the presence of joint laxity and thinning ofthe fingers. SEMD leptodactylic type is a rare skeletaldysplasia, and we hope that by raising awareness, we can contribute to a better understanding of this condition."

Movement Disorders • Musculoskeletal Diseases • Orthopedics • IGF1 • IGFBP3

Identification of two critical amino acid residues in short-chain aldehyde-responsive odorant receptors. (PubMed, J Biochem) - "While Olfr732-type ORs are conserved across species, Olfr733-types, unique to specific rodents, appear to have evolved from Olfr732, with Pro148 enhancing membrane expression and aldehyde sensitivity. Mouse ORs with ProBW4.49 tend to exhibit improved membrane expression compared to their paralogs, especially when co-expressed with RTP1S. This study concludes that the Pro residue in the fourth transmembrane domain significantly contributes to the structural stability of certain olfactory receptors, highlighting the intricate molecular mechanisms underlying OR functionality and evolution."

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