G59S mutation in theGJB2 (connexin 26) gene in a patient with Bart-Pumphrey syndrome

Alexandrino, Fabiana; Sartorato, Edi Lúcia; Marques-de-Faria, Antônia Paula; Steiner, Carlos Eduardo

doi:10.1002/ajmg.a.30822

Cited by 35 publications

(32 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These mutations include ΔE42 (PPK), G59A (PPK), D66H (VS) and R75W (PPK) [45, 46]. Of these, G59S is also associated with both VS and BPS [47]. N54 is also associated with BPS or PPK, depending on whether it is mutated to a K or H, respectively [48, 49].…”

Section: Connexin Phenotypes Affecting the Ear And Epidermismentioning

confidence: 99%

The role of connexins in ear and skin physiology — Functional insights from disease-associated mutations

Nicholson

2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

116

123

View full text Add to dashboard Cite

Defects in several different connexins have been associated with several different diseases. The most common of these is deafness, where a few mutations in connexin (Cx) 26 have been found to contribute to over 50% of the incidence of non-syndromic deafness in different human populations. Other mutations in Cx26 or Cx30 have also been associated with various skin phenotypes linked to deafness (PPK, BPS, VS, KID, etc.). The large array of disease mutants offer unique opportunities to gain insights into the underlying function of gap junction proteins and their channels in the normal and pathogenic physiology of the cochlea and epidermis. This review focuses on those mutants where the impact on channel function has been assessed, and correlated with the disease phenotype, or organ function in knock-out mouse models. These approaches have provided evidence supporting a role of gap junctions and hemichannels in K+ removal and recycling in the ear, as well as possible roles for nutrient passage, in the cochlea. In contrast, increases in hemichannel opening leading to increased cell death, was associated with several KID skin disease/hearing mutants. In addition to providing clues for therapeutic strategies, these findings allow us to better understand the specific functions of connexin channels that are important for normal tissue function.

show abstract

Section: Connexin Phenotypes Affecting the Ear And Epidermismentioning

confidence: 99%

The role of connexins in ear and skin physiology — Functional insights from disease-associated mutations

Nicholson

2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

116

123

View full text Add to dashboard Cite

show abstract

“…Mutations in GJB2 were later discovered and were shown to cause up to 50% of cases with ARNSHL in Caucasian populations while their frequency is much lower in some other parts of the world (7,8,9). GJB2 mutations can also cause autosomal dominant nonsyndromic hearing loss (ADNSHL) (4), and autosomal dominantly inherited Keratitis-Ichthyosis-Deafness (MIM 148210), (10,11), Vohwinkel (MIM 124500) (12,13), Bart-Pumphrey (MIM 149200) (13,14) syndromes and Palmoplantar Keratoderma-Deafness (MIM 148350). More than 200 different mutations have been identified in this single coding exon gene and recurrent mutations, almost specific to a population, have been observed (Human Gene Mutation Database Professional Edition, accessed in June 2010).…”

Section: Genes Implicated In Cochlear Homeostasismentioning

confidence: 99%

Autosomal recessive nonsyndromic deafness genes: a review

Duman¹

2012

Front Biosci

131

104

View full text Add to dashboard Cite

More than 50 percent of prelingual hearing loss is genetic in origin, and of these up to 93 percent are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only finding and is referred to as nonsyndromic deafness. To date, more than 700 different mutations have been identified in one of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the most common cause of hearing loss in many populations. Other relatively common deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this report we summarize genes and mutations reported in families with ARNSHL. Founder effects were demonstrated for some recurrent mutations but the most significant findings are the extreme locus and allelic heterogeneity and different spectrum of genes and mutations in each population.

show abstract

“…This substitution was not found in the unaffected family members or healthy controls, excluding the polymorphism in the GJB2 gene. This mutation has been reported in a case of BPS in 2005 and atypical VS in 2006 . Dominant negative alterations in the E1 domain of CX26 affect both protein transport and channel permeability .…”

Section: Discussionmentioning

confidence: 82%

G59S mutation in the GJB2 gene in a Chinese family with classic Vohwinkel syndrome

Xie¹,

Yang

Luo

et al. 2018

The Journal of Dermatology

View full text Add to dashboard Cite

Vohwinkel syndrome (VS) is a rare autosomal dominant condition, also known as mutilating palmoplantar keratoderma accompanied by sensorineural deafness. The LOR and GJB2 genes are reported to be responsible for VS. The GJB2 gene encodes connexin 26, a component of intercellular gap junctions expressed in various tissues. We report the case of a 31‐year‐old Chinese woman with classic VS characterized by sensorineural deafness and mutilating palmoplantar keratoderma. Further genetic studies demonstrated a nucleotide change (c.175G>A) in the GJB2 gene, leading to an amino acid alteration (G59S). This identical missense mutation (G59S) has also been reported in a patient with Bart–Pumphrey syndrome. Together with our findings and previous studies, we conclude that the identical mutation (G59S) in the GJB2 gene contributes to various manifestations.

show abstract

G59S mutation in theGJB2 (connexin 26) gene in a patient with Bart-Pumphrey syndrome

Cited by 35 publications

References 21 publications

The role of connexins in ear and skin physiology — Functional insights from disease-associated mutations

The role of connexins in ear and skin physiology — Functional insights from disease-associated mutations

Autosomal recessive nonsyndromic deafness genes: a review

G59S mutation in the GJB2 gene in a Chinese family with classic Vohwinkel syndrome

Contact Info

Product

Resources

About