A Connexin Gene (GJB3) Mutation in a Chinese Family With Erythrokeratodermia Variabilis, Ichthyosis and Nonsyndromic Hearing Loss: Case Report and Mutations Update

Abstract

Background: Gap junctions formed by connexins are channels on cytoplasm functioning in ion recycling and homeostasis. Some members of connexin family including connexin 31 are significant components in human skin and cochlea. In clinic, mutations of connexin 31 have been revealed as the cause of a rare hereditary skin disease called erythrokeratodermia variabilis (EKV) and non-syndromic hearing loss (NSHL).Objective: To determine the underlying genetic cause of EKV, ichthyosis and NSHL in three members of a Chinese pedigree and skin histologic characteristics of the EKV patient.Methods: By performing whole exome sequencing (WES), Sanger sequencing and skin biopsy, we demonstrate a Chinese pedigree carrying a mutation of GJB3 with three patients separately diagnosed with EKV, ichthyosis and NSHL.Results: The proband, a 6-year-old Chinese girl, presented with demarcated annular red-brown plaques and hyperkeratotic scaly patches on her trunk and limbs. Her mother has ichthyosis with hyperkeratosis and geographic tongue while her younger brother had NSHL since birth. Mutation analysis revealed all of them carried a heterozygous missense mutation c.293G>A of GJB3. Skin biopsy showed many grain cells with dyskeratosis in the granular layer. Acanthosis, papillomatosis, and a mild superficial perivascular lymphocytic infiltrate were observed.Conclusion: A mutation of GJB3 associated with EKV, ichthyosis and NSHL is reported in this case. The daughter with EKV and the son with NSHL in this Chinese family inherited the mutation from their mother with ichthyosis. The variation of clinical features may involve with genetic, epigenetic and environmental factors.

The Association Between Mitochondrial tRNAGlu Variants and Hearing Loss: A Case-Control Study

“… 22 The primers for GJB3 were: forward-5’- GTC ACC TAT TCA TTC ATA CGA TGG-3’ and reverse-5’-TCA CTC AGC CCC TGT AGG AC-3’. 23 The primer sequences for amplification of the GJB6 were: forward-5’-CCT TAA AAT AAA GTT GGC TTC AG-3’, reverse-5’-GGA ACT TTC AGG TTG GTA TTG-3’. 24 The primer sequences for TRMU were: forward-5’- ACA GCG CAG AAG AAG AGC AGT-3’, reverse-5’- ACA ACG CCA CGA CGG ACG-3’.…”

Impairment of α-tubulin and F-actin interactions of GJB3 induces aneuploidy in urothelial cells and promotes bladder cancer cell invasion

“…For instance, well-characterized mutations in the connexin gap junction alpha-1 (GJA1, also known as Cx43), which is expressed highly in normal cardiac myocytes and osteoblasts [ 9 ], have been shown to result in congenital cardiac abnormalities and impairments in bone development [ 10 , 11 ]. Similarly, GJB3 is highly expressed in skin, cochlear, and bladder cells [ 12 ] and mutations in this protein have been associated with non-syndromic hearing loss in humans and keratinocyte hyperproliferation in transgenic mouse models [ 13 ].…”

“…Testing for GJA1 levels thus may have utility in the prognostic stratification among patients with high-risk NMIBC. While GBJ3 expression in bladder tissue has been reported [ 12 ], virtually nothing is known about the physiological role of GJB3 in bladder tissue or its possible involvement in the onset and dissemination of BC. Given the findings that aneuploidy increases with bladder cancer progression and that the vast majority (up to 90%) of MIBC exhibit a high degree of aneuploidy [ 25 , 26 ], and the observations showing that DNA ploidy provides predictive characteristics for the survival of patients with BC, it is appealing to investigate the role of GJB3 in BC [ 27 ].…”