Published online Feb 26, 2023. doi: 10.12998/wjcc.v11.i6.1403
Peer-review started: November 10, 2022
First decision: December 13, 2022
Revised: December 26, 2022
Accepted: February 7, 2023
Article in press: February 7, 2023
Published online: February 26, 2023
Processing time: 105 Days and 19.6 Hours
We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia (HED) with a variation in GJB6 (c.31G>A). The patients in the family had a triad of clinical manifestations of varying degrees. Although the same variation locus have been reported, the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder, palmoplantar keratosis, and congenital hypotrichosis.
This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED. The proband (IV4) was a male patient with normal sweat gland function and dental development, no skeletal dysplasia, no cognitive disability, and no hearing impairments. His parents were not consanguineously married. Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longitudinal ridges, in addition to mild bilateral palmoplantar hyperkeratosis. GJB6, GJB2, and GJA1 have been reported to be the causative genes of HED; therefore, we subjected the patient’s samples to Sanger sequencing of these three genes. In this family, the variation locus was at GJB6 (c.31G>A, p.Gly11Arg). Overexpression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models, and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot, respectively.
We report another HED phenotype associated with GJB6 variations, which can help clinicians to diagnose HED despite its varying presentations.
Core Tip: We report on a Chinese family with hidrotic ectodermal dysplasia (HED), with patients in the family presenting varying degrees of hair dysplasia, nail dysplasia, and palmoplantar hyperkeratosis. In addition, we performed a literature review of other reported HED genotypes and their corresponding phenotypes, which lays a foundation for subsequent studies on these associations. Overexpression vectors of the GJB6 gene and its variants (variation sites: c.31G>A, c.263C>T, c.110T>A) were established and transfected into a HaCaT cell model. The expression changes of related mRNA and proteins before and after gene editing were obtained by real-time reverse transcriptase-polymerase chain reaction and Western blot, respectively, to provide clues for subsequent pathogenesis studies.