Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma

Pandey, Nishtha; Xavier, Dennis F.; Chatterjee, Arunima; Mani, Ram S.; Hiremagalore, Ravi; Tharakan, Ajith; Rajashekhar, Bellur; Anand, Anuranjan

doi:10.1111/ahg.12141

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…The material exchange and information exchange between adjacent cells are important functions of connexin. Part of the mutations listed in Table 1 have been confirmed to affect the permeability changes of cells to ions or other molecules in vitro [ 29 , 50 , 61 , 65 , 66 , 73 ]. Therefore, the abnormal traffic pathways and subcellular localization of mutated connexin may be important for the pathological processes of diseases such as hearing loss [ 26 , 30 , 79 , 80 , 81 , 82 ].…”

Section: Cxs Mutations Induced Dysfunction and Abnormal Trafficking P...mentioning

confidence: 99%

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

Zong

Liu

et al. 2023

IJMS

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The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6, respectively, are the most abundantly expressed connexins in the inner ear. Connexin 43, which is encoded by GJA1, appears to be widely expressed in various organs, including the heart, skin, the brain, and the inner ear. The mutations that arise in GJB2, GJB6, and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can properly operate. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of these connexins, the existing controversies in the trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness.

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Section: Cxs Mutations Induced Dysfunction and Abnormal Trafficking P...mentioning

confidence: 99%

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

Zong

Liu

et al. 2023

IJMS

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“…This syndrome is not commonly associated with deafness. However, two mutations (p.Asn54Lys and p.Gly59Arg) in the GJB6 gene have recently been reported to result in palmoplantar keratoderma with hearing loss [167,168]. Additionally, a GJB2 gene mutation (Cx26 p.Asn14Lys) identified in a Dutch child led to a phenotype resembling Clouston syndrome accompanied with deafness [169].…”

Section: Connexin Mutations and Hereditary Skin Diseasesmentioning

confidence: 99%

Connexin Mutations and Hereditary Diseases

Qiu

Zheng

Chen

et al. 2022

IJMS

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Inherited diseases caused by connexin mutations are found in multiple organs and include hereditary deafness, congenital cataract, congenital heart diseases, hereditary skin diseases, and X-linked Charcot–Marie–Tooth disease (CMT1X). A large number of knockout and knock-in animal models have been used to study the pathology and pathogenesis of diseases of different organs. Because the structures of different connexins are highly homologous and the functions of gap junctions formed by these connexins are similar, connexin-related hereditary diseases may share the same pathogenic mechanism. Here, we analyze the similarities and differences of the pathology and pathogenesis in animal models and find that connexin mutations in gap junction genes expressed in the ear, eye, heart, skin, and peripheral nerves can affect cellular proliferation and differentiation of corresponding organs. Additionally, some dominant mutations (e.g., Cx43 p.Gly60Ser, Cx32 p.Arg75Trp, Cx32 p.Asn175Asp, and Cx32 p.Arg142Trp) are identified as gain-of-function variants in vivo, which may play a vital role in the onset of dominant inherited diseases. Specifically, patients with these dominant mutations receive no benefits from gene therapy. Finally, the complete loss of gap junctional function or altered channel function including permeability (ions, adenosine triphosphate (ATP), Inositol 1,4,5-trisphosphate (IP3), Ca2+, glucose, miRNA) and electric activity are also identified in vivo or in vitro.

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Cytomembrane Trafficking Pathways of Connexin 26, 30 and 43: Recent Updates

Zong¹,

Liu²,

Tu³

et al. 2023

Preprint

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The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6 respectively, are the most abundant expressed connexins in the inner ear. Connexin 43 which is encoded by GJA1 appears to be widely expressed in various organs, including the heart, skin, brain, and inner ear. The mutations that arise in GJB2, GJB6 and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can operate properly. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of connexin 26, the existing controversies in trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness.

show abstract

Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma

Cited by 3 publications

References 38 publications

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

Connexin Mutations and Hereditary Diseases

Cytomembrane Trafficking Pathways of Connexin 26, 30 and 43: Recent Updates

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