scholarly journals GJA1mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype

2009 ◽  
Vol 30 (5) ◽  
pp. 724-733 ◽  
Author(s):  
William A. Paznekas ◽  
Barbara Karczeski ◽  
Sascha Vermeer ◽  
R. Brian Lowry ◽  
Martin Delatycki ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Oculodentodigital Dysplasia

scholarly journals Structure and functional studies of N-terminal Cx43 mutants linked to oculodentodigital dysplasia

2012 ◽  
Vol 23 (17) ◽  
pp. 3312-3321 ◽  
Author(s):  
Qing Shao ◽  
Qin Liu ◽  
Robert Lorentz ◽  
Xiang-Qun Gong ◽  
Donglin Bai ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Connexin 43 ◽  
Protein Structure Determination ◽  
Helical Structure ◽  
Dominant Negative ◽  
Negative Effects ◽  
Gene Encoding ◽  
Functional Studies ◽  
Α Helix ◽  
Oculodentodigital Dysplasia

Mutations in the gene encoding connexin-43 (Cx43) cause the human development disorder known as oculodentodigital dysplasia (ODDD). In this study, ODDD-linked Cx43 N-terminal mutants formed nonfunctional gap junction–like plaques and exhibited dominant-negative effects on the coupling conductance of coexpressed endogenous Cx43 in reference cell models. Nuclear magnetic resonance (NMR) protein structure determination of an N-terminal 23–amino acid polypeptide of wild-type Cx43 revealed that it folded in to a kinked α-helical structure. This finding predicted that W4 might be critically important in intramolecular and intermolecular interactions. Thus we engineered and characterized a W4A mutant and found that this mutant formed a regular, nonkinked α-helix but did not form functional gap junctions. Furthermore, a G2V variant peptide of Cx43 showed a kinked helix that now included V2 interactions with W4, resulting in the G2V mutant forming nonfunctional gap junctions. Also predicted from the NMR structures, a G2S mutant was found to relieve these interactions and allowed the protein to form functional gap junctions. Collectively, these studies suggest that the nature of the mutation conveys loss of Cx43 function by distinctly different mechanisms that are rooted in the structure of the N-terminal region.

Palmoplantar keratosis in oculodentodigital dysplasia with aGJA1point mutation out of the C-terminal region of connexin 43

2014 ◽  
Vol 41 (12) ◽  
pp. 1095-1097 ◽  
Author(s):  
Toshiaki Kogame ◽  
Teruki Dainichi ◽  
Yutaka Shimomura ◽  
Miki Tanioka ◽  
Kenji Kabashima ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Terminal Region ◽  
Palmoplantar Keratosis ◽  
Oculodentodigital Dysplasia

scholarly journals Oculodentodigital Dysplasia: A Case Report and Major Review of the Eye and Ocular Adnexa Features of 295 Reported Cases

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Virang Kumar ◽  
Natario L. Couser ◽  
Arti Pandya
Keyword(s):  
Systematic Review ◽  
Case Report ◽  
Connexin 43 ◽  
Genetic Disorder ◽  
Extensive Literature ◽  
Missense Mutations ◽  
Multiple Congenital Anomalies ◽  
Ocular Adnexa ◽  
Major Review ◽  
Oculodentodigital Dysplasia

Oculodentodigital dysplasia (ODDD) is a rare genetic disorder associated with a characteristic craniofacial profile with variable dental, limb, eye, and ocular adnexa abnormalities. We performed an extensive literature review to highlight key eye features in patients with ODDD and report a new case of a female patient with a heterozygous missense GJA1 mutation (c.65G>A, p.G22E) and clinical features consistent with the condition. Our patient presented with multiple congenital anomalies including syndactyly, microphthalmia, microcornea, retrognathia, and a small nose with hypoplastic alae and prominent columella; in addition, an omphalocele defect was present, which has not been reported in previous cases. A systematic review of the published cases to date revealed 91 literature reports of 295 individuals with ODDD. There were 73 different GJA1 mutations associated with these cases, of which the most common were the following missense mutations: c.605G>A (p.R202H) (11%), c.389T>C (p.I130T) (10%), and c.119C>T (p.A40V) (10%). Mutations most commonly affect the extracellular-1 and cytoplasmic-1 domains of connexin-43 (gene product of GJA1), predominately manifesting in microphthalmia and microcornea. The syndrome appears with an approximately equal sex ratio. The most common eye features reported among all mutations were microcornea, microphthalmia, short palpebral fissures, and glaucoma.

A NewGJA1(Connexin 43) Mutation Causing Oculodentodigital Dysplasia Associated to Uncommon Features

2007 ◽  
Vol 28 (4) ◽  
pp. 198-202 ◽  
Author(s):  
David Rivera de la Parra ◽  
Juan Carlos Zenteno
Keyword(s):  
Connexin 43 ◽  
Oculodentodigital Dysplasia

Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse

2011 ◽  
Vol 300 (4) ◽  
pp. H1402-H1411 ◽  
Author(s):  
Jari M. Tuomi ◽  
Karel Tyml ◽  
Douglas L. Jones
Keyword(s):  
Connexin 43 ◽  
Atrial Tachycardia ◽  
Programmed Electrical Stimulation ◽  
Activation Patterns ◽  
Gap Junction Channels ◽  
Refractory Periods ◽  
Clinical Observations ◽  
Electrophysiological Studies ◽  
Oculodentodigital Dysplasia

Atrial fibrillation (AF), the most common cardiac arrhythmia seen in general practice, can be promoted by conduction slowing. Cardiac impulse conduction depends on gap junction channels, which are composed of connexins (Cxs). While atrial Cx40 and Cx43 are equally expressed, AF studies have primarily focused on Cx40 reductions. The G60S Cx43 mutant (Cx43G60S/+) mouse model of Oculodentodigital dysplasia has a 60% reduction in Cx43 in the atria. Cx43G60S/+ mice were compared with Cx40-deficient (Cx40−/−) mice to determine the role of Cxs in atrial tachycardia/fibrillation (AT/F). Intracardiac electrophysiological studies were done in 6-mo-old male C57BL/6 Cx43G60S/+ mutant, littermate (Cx43+/+), Cx40−/−, and C57BL/6 wild-type (WT) mice. AT/F induction used an extra stimulus during sinus rhythm, programmed electrical stimulation, or burst pacing (1-ms pulses, 50-Hz, 400-ms train) in the absence and presence of carbachol (CCh). Atrial effective refractory periods did not differ between strains. Cx43G60S/+ mice were more susceptible to induction of sustained AT/F (duration >2 min, 9 of 12; maximum >35 min) compared with Cx43+/+ mice (3 of 11; χ2 = 5.24; P = 0.02). CCh enhanced sustained AT/F susceptibility in WT (from 1 of 12 without, to 7 of 10 with CCh; χ2 = 8.98; P < 0.01) but not in Cx40−/− mice (1 of 13 without vs. 2 of 9 with CCh; χ2 = 0.95; P = NS). The pattern of epicardial recordings during AT/F in Cx43G60S/+ mice was left preceding right, with left atrial fractionated activation patterns consistent with clinical observations of AF. In conclusions, while Cx43G60S/+ mice had severe AT/F, Cx40−/− mice were resistant to CCh-induced AT/F.

scholarly journals Ocular manifestations in oculodentodigital dysplasia resulting from a heterozygous missense mutation (L113P) in GJA1 (connexin 43)

Eye ◽  
2008 ◽  
Vol 23 (3) ◽  
pp. 549-555 ◽  
Author(s):  
F U Musa ◽  
P Ratajczak ◽  
J Sahu ◽  
S Pentlicky ◽  
A Fryer ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Connexin 43 ◽  
Heterozygous Missense Mutation ◽  
Ocular Manifestations ◽  
Oculodentodigital Dysplasia

scholarly journals Connexin 43 (GJA1) Mutations Cause the Pleiotropic Phenotype of Oculodentodigital Dysplasia

2003 ◽  
Vol 72 (2) ◽  
pp. 408-418 ◽  
Author(s):  
William A. Paznekas ◽  
Simeon A. Boyadjiev ◽  
Robert E. Shapiro ◽  
Otto Daniels ◽  
Bernd Wollnik ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Pleiotropic Phenotype ◽  
Oculodentodigital Dysplasia

Oculodentodigital Dysplasia: Disease Spectrum in an Eight-year-old Boy, His Parents and a Sibling

2009 ◽  
Vol 33 (4) ◽  
pp. 337-341 ◽  
Author(s):  
Naser Asl Aminabadi ◽  
Azin Taghizadeh Ganji ◽  
Ali Vafaei ◽  
Maryam Pourkazemi ◽  
Sina Ghertasi Oskouei
Keyword(s):  
Connexin 43 ◽  
Primary Teeth ◽  
Permanent Teeth ◽  
Cns Involvement ◽  
Disease Spectrum ◽  
First Case ◽  
Characteristic Features ◽  
Tip Of The Tongue ◽  
Oculodentodigital Dysplasia ◽  
Ocular Signs

Oculodentodigital dysplasia is an extremely rare autosomal dominant pleiotropic disorder, caused by mutations in the Connexin 43 gene (GJA1). Described here is a previously undiagnosed case of an 8-year-old boy with enamel and dentin hypoplasia and typical faces. In this presentation, many typical clinical and radiographical features of this condition are present. The characteristic features include a typical face, premature loss of primary teeth and odontodysplasia of permanent teeth, clinodactyly, ocular signs,and CNS involvement. To our knowledge, the case that we report here is the first case with mamelon-shaped tip of the tongue and enlarged midpalatal raphe.

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