Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Hum Mutat
2019 Feb 01;402:217-229. doi: 10.1002/humu.23686.
Show Gene links
Show Anatomy links
A novel autosomal recessive GJB2-associated disorder: Ichthyosis follicularis, bilateral severe sensorineural hearing loss, and punctate palmoplantar keratoderma.
Youssefian L, Vahidnezhad H, Saeidian AH, Mahmoudi H, Karamzadeh R, Kariminejad A, Huang J, Li L, Jannace TF, Fortina P, Zeinali S, White TW, Uitto J.
???displayArticle.abstract???
Ichthyosis follicularis, a distinct cutaneous entity reported in combination with atrichia, and photophobia has been associated with mutations in MBTPS2. We sought the genetic cause of a novel syndrome of ichthyosis follicularis, bilateral severe sensorineural hearing loss and punctate palmoplantar keratoderma in two families. We performed whole exome sequencing on three patients from two families. The pathogenicity and consequences of mutations were studied in the Xenopus oocyte expression system and by molecular modeling analysis. Compound heterozygous mutations in the GJB2 gene were discovered: a pathogenic c.526A>G; p.Asn176Asp, and a common frameshift mutation, c.35delG; p.Gly12Valfs*2. The p.Asn176Asp missense mutation was demonstrated to significantly reduce the cell-cell gap junction channel activity and increase the nonjunctional hemichannel activity in the Xenopus oocyte expression system. Molecular modeling analyses of the mutant Cx26 protein revealed significant changes in the structural characteristics and electrostatic potential of the Cx26, either in hemichannel or gap junction conformation. Thus, association of a new syndrome of an autosomal recessive disorder of ichthyosis follicularis, bilateral severe sensorineural hearing loss and punctate palmoplantar keratoderma with mutations in GJB2, expands the phenotypic spectrum of the GJB2-associated disorders. The findings attest to the complexity of the clinical consequences of different mutations in GJB2.
???displayArticle.pubmedLink???
30431684 ???displayArticle.pmcLink???PMC6481180 ???displayArticle.link???Hum Mutat ???displayArticle.grants???[+]
R01 EY013163 National Eye Institute, R01 EY026911 National Eye Institute, R01 EY013163 NEI NIH HHS , R01 EY026911 NEI NIH HHS
Akiyama,
A novel GJB2 mutation p.Asn54His in a patient with palmoplantar keratoderma, sensorineural hearing loss and knuckle pads.
2007, Pubmed
Akiyama,
A novel GJB2 mutation p.Asn54His in a patient with palmoplantar keratoderma, sensorineural hearing loss and knuckle pads.
2007,
Pubmed Bandyopadhyay,
Porokeratotic eccrine ostial and dermal duct nevus.
2015,
Pubmed Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991,
Pubmed
,
Xenbase Bruzzone,
Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins.
1993,
Pubmed
,
Xenbase Denoyelle,
Connexin 26 gene linked to a dominant deafness.
1998,
Pubmed de Vries,
The HADDOCK web server for data-driven biomolecular docking.
2010,
Pubmed Dolinsky,
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations.
2004,
Pubmed Donnelly,
Differential susceptibility of Cx26 mutations associated with epidermal dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus epidermidis.
2012,
Pubmed Easton,
Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations.
2012,
Pubmed Eskin-Schwartz,
Somatic Mosaicism for a "Lethal" GJB2 Mutation Results in a Patterned Form of Spiny Hyperkeratosis without Eccrine Involvement.
2016,
Pubmed Eswar,
Comparative protein structure modeling using MODELLER.
2007,
Pubmed Evans,
The gap junction cellular internet: connexin hemichannels enter the signalling limelight.
2006,
Pubmed Gerido,
Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness.
2007,
Pubmed
,
Xenbase González,
Species specificity of mammalian connexin-26 to form open voltage-gated hemichannels.
2006,
Pubmed
,
Xenbase Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed Jonard,
A familial case of Keratitis-Ichthyosis-Deafness (KID) syndrome with the GJB2 mutation G45E.
2008,
Pubmed Karademir,
Engineered Cx26 variants established functional heterotypic Cx26/Cx43 and Cx26/Cx40 gap junction channels.
2016,
Pubmed Koval,
Mix and match: investigating heteromeric and heterotypic gap junction channels in model systems and native tissues.
2014,
Pubmed Laird,
Life cycle of connexins in health and disease.
2006,
Pubmed Lazic,
Extending the phenotypic spectrum of keratitis-ichthyosis-deafness syndrome: report of a patient with GJB2 (G12R) Connexin 26 mutation and unusual clinical findings.
2012,
Pubmed Leclère,
GJB2 mutations: Genotypic and phenotypic correlation in a cohort of 690 hearing-impaired patients, toward a new mutation?
2017,
Pubmed Lee,
Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes.
2009,
Pubmed
,
Xenbase Levinsohn,
A Somatic p.G45E GJB2 Mutation Causing Porokeratotic Eccrine Ostial and Dermal Duct Nevus.
2015,
Pubmed Li,
Fast and accurate long-read alignment with Burrows-Wheeler transform.
2010,
Pubmed Lilly,
Connexin channels in congenital skin disorders.
2016,
Pubmed Maeda,
Structure of the connexin 26 gap junction channel at 3.5 A resolution.
2009,
Pubmed Marsden,
Comedo naevus of the palm--a sweat duct naevus?
1979,
Pubmed McKenna,
The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.
2010,
Pubmed Meşe,
Altered gating properties of functional Cx26 mutants associated with recessive non-syndromic hearing loss.
2004,
Pubmed
,
Xenbase Mhaske,
The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity.
2013,
Pubmed
,
Xenbase Minami,
GJB2-associated hearing loss undetected by hearing screening of newborns.
2013,
Pubmed Oeffner,
IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.
2009,
Pubmed Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed Ripps,
Properties of connexin26 hemichannels expressed in Xenopus oocytes.
2004,
Pubmed
,
Xenbase Rouan,
trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation.
2001,
Pubmed
,
Xenbase Sanchez,
The D50N mutation and syndromic deafness: altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions.
2013,
Pubmed
,
Xenbase Sánchez,
Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome.
2010,
Pubmed
,
Xenbase Snoeckx,
GJB2 mutations and degree of hearing loss: a multicenter study.
2005,
Pubmed Spray,
Equilibrium properties of a voltage-dependent junctional conductance.
1981,
Pubmed
,
Xenbase Srinivas,
Human diseases associated with connexin mutations.
2018,
Pubmed Stong,
A novel mechanism for connexin 26 mutation linked deafness: cell death caused by leaky gap junction hemichannels.
2006,
Pubmed Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase Wang,
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.
2010,
Pubmed White,
Mouse Cx50, a functional member of the connexin family of gap junction proteins, is the lens fiber protein MP70.
1992,
Pubmed
,
Xenbase Word,
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation.
1999,
Pubmed Zonta,
The p.Cys169Tyr variant of connexin 26 is not a polymorphism.
2015,
Pubmed
