ICD10 Code = Q82.8
沃溫克爾症候群
Genomic coordinate (human 13:20,187,470 GJB2).
Cytoband (human 13q12.11 GJB2).
OMIM’ genes @ 13q12.11 = 22 genes.
ClinVar = 524 GJB2 variants reported.
PANTHER Classification is PTHR11227.
Cytoband Structure: WCWCCWG6BGBGB2GB2
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Here I 🎁 present: “Vohwinkel Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966.
INTRODUCTION.
The ABOVE diagram illustrates the structure, cellular assembly, and disease-associated mutations of Connexin-26 (Cx26), a gap junction protein encoded by the GJB2 gene.
Key Elements’ of the Diagram.
Panel A (Cellular Pathway): Shows how individual connexin proteins are synthesized and processed through the Endoplasmic Reticulum (ER) and Golgi Apparatus (GA). They are transported to the plasma membrane, where they assemble into a hexameric structure called a hemichannel (HC) or connexon. When hemichannels from adjacent cells (Cell 1 and Cell 2) dock back-to-back, they form a gap junction (GJ) channel, organizing into a larger gap junction plaque to facilitate direct intercellular communication.
Panel B (Cx-Hemichannel Regulation): Details a single hemichannel composed of six connexin subunits. These surface channels are tightly gated and regulated by factors such as extracellular pH, membrane voltage, and calcium ions.
Panel C (Connexin-26 Membrane Topology & Mutations): Depicts the secondary structure of a single Cx26 subunit spanning across the plasma membrane:Intracellular Domain: Includes the Amino Terminus (NT), Cytoplasmic Loop (CL), and Carboxy Terminus (CT).Transmembrane Domains: Consists of four helices (TM1, TM2, TM3, TM4).Extracellular Domain: Consists of two loops (E1 and E2) involved in docking with hemichannels from opposing cells.
Mutations: Highlights various amino acid substitutions linked to clinical conditions. Mutations colored in red (e.g., G11E, G12R, N14K/Y, S17F, A40V, ΔE42, G45E, A88V) and blue (e.g., D50N/A/Y, N54K, G59S/A/R, Y65H, D66H, H73R, R75W/Q, G130V, F142L, S183F) are associated with hereditary disorders, such as syndromic deafness (e.g., Keratitis-Ichthyosis-Deafness or KID syndrome) or non-syndromic hearing loss, and Vohwinkel Syndrome.
