Abstract | BACKGROUND: METHOD: Rat epidermal keratinocytes were transfected with cDNA encoding wildtype Cx26 and/or the Met34Lys mutant of Cx26. Fixed cells were immunolabeled in order to assess the subcellular location of the Cx26 mutant and cell images were captured. RESULTS: Expression in rat epidermal keratinocytes revealed that the Met34Lys mutant was retained in the endoplasmic reticulum, unlike wildtype Cx26, and failed to reach the plasma membrane to form gap junctions. Additionally, the Met34Lys mutant acted dominantly to wildtype Cx26, restricting its delivery to the cell surface. CONCLUSION: Overall, we show the p.Met34Lys variant is a novel dominant acting variant causing PPK with deafness. The presence of a loss a function variant on the other allele creates a more severe clinical phenotype, with some features reminiscent of KID syndrome.
|
Authors | Emma C Bedoukian, Stefan Rentas, Cara Skraban, Qing Shao, James Treat, Dale W Laird, Kathleen E Sullivan |
Journal | Molecular genetics & genomic medicine
(Mol Genet Genomic Med)
Vol. 9
Issue 2
Pg. e1574
(02 2021)
ISSN: 2324-9269 [Electronic] United States |
PMID | 33443819
(Publication Type: Case Reports, Journal Article)
|
Copyright | © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. |
Chemical References |
- GJB2 protein, human
- Connexin 26
|
Topics |
- Adult
- Cells, Cultured
- Connexin 26
(genetics, metabolism)
- Deafness
(genetics, pathology)
- Female
- Frameshift Mutation
- Humans
- Keratinocytes
(metabolism)
- Keratoderma, Palmoplantar
(genetics, pathology)
- Mutation, Missense
- Phenotype
- Protein Transport
|