A Novel GJA1 Mutation in Oculodentodigital Dysplasia with Progressive Spastic Paraplegia and Sensory Deficits

Furuta, Natsumi; Ikeda, Masaki; Hirayanagi, Kimitoshi; Fujita, Yukio; Amaki, Makoto; Okamoto, Koichi

doi:10.2169/internalmedicine.51.5770

Cited by 21 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…23,[26][27][28][29]40,46,47 In the present study, OAG is present in seven of the eight individuals (87.5%) with the GJA1 mutation, which is a significantly higher association than that reported in previous studies.…”

contrasting

confidence: 44%

See 1 more Smart Citation

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family

Huang

Wang

Xiao

et al. 2015

Eye

View full text Add to dashboard Cite

Purpose To identify genetic defects in a large family with open angle glaucoma (OAG) and microcornea. Methods Genomic DNA was prepared from leukocytes of 15 individuals from three generations of a Chinese family, including seven individuals with OAG and microcornea, one with microcornea alone, and seven healthy individuals. Whole exome sequencing was performed on genomic DNA of the proband. Candidate variants were obtained through multiple steps of bioinformatics analysis and validated by Sanger sequencing and segregation analysis. Results Exome sequencing detected a candidate variant in GJA1, a novel truncation mutation (c.791_792delAA, p.K264Ifs*43). This mutation was present in all seven individuals with OAG and microcornea and the individual with microcornea alone, but not in the seven unaffected relatives in the family. It was not present in 1394 alleles from 505 unrelated controls without glaucoma and 192 normal controls. Extraocular signs were not observed in seven out of the eight individuals; only one was affected with dental enamel hypoplasia and syndactyly. Conclusions A novel truncation mutation in GJA1 is associated with OAG and microcornea in a Chinese family. This suggests that GJA1 should be included as a candidate gene for glaucoma.

show abstract

contrasting

confidence: 44%

“…Glaucoma has been recorded in 33 of 161 patients with ODDD and GJA1 mutations but in none of the 33 patients with other conditions and GJA1 mutations. 23,[26][27][28][29][30][31]37,40,46,47 These glaucoma-associated mutations distribute randomly in the functional domains of GJA1. It total, glaucoma is reported in~17% of patients (33/194) with GJA1 mutations.…”

mentioning

confidence: 99%

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family

Huang

Wang

Xiao

et al. 2015

Eye

View full text Add to dashboard Cite

show abstract

“…Ataxia is a cerebellar phenomenon that manifests as a lack of voluntary muscle coordination, typically observed as disturbances in the gait pattern. Interestingly, one patient carrying the W25C (TM1) mutation presented with all characteristic craniofacial features and extremity anomalies, as well as with spastic tetraparesis, hyperreflexia and sensory disturbances (numbness in feet), indicating wide-spread sensori-motor neurological deficits (Furuta et al, 2012). In two siblings characterized for having an R33X mutation, myelination deficits were described (Joss et al, 2008).…”

Section: Neurological Phenotype In Oddd - Link To Aberrant Cx43 Channelsmentioning

confidence: 99%

“…MRI imaging studies have brought up diffuse bilateral abnormalities in the subcortical cerebral white matter, possibly indicating a slow progressive leukodystrophy. Mental retardation may occur but is rare (Paznekas et al, 2003, 2009; Amador et al, 2008; Joss et al, 2008; Furuta et al, 2012). Of note, in most families, the appearance of neurological symptoms is unpredictable, but in 4 families genotyped for having the L90V, L113P, K134N, or G138R mutant, all ODDD patients exhibit neurological traits (Paznekas et al, 2009).…”

Section: Introduction: Oddd Mutations Clinical Manifestations and Rementioning

confidence: 99%

Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?

et al. 2013

View full text Add to dashboard Cite

The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell–cell transfer of metabolic and electric signals. GJs are formed by connexins of which Cx43 is most widespread in the human body. In the brain, Cx43 GJs are mostly found in astroglia where they coordinate the propagation of Ca2+ waves, spatial K+ buffering, and distribution of glucose. Beyond its role in direct intercellular communication, Cx43 also forms unapposed, non-junctional hemichannels in the plasma membrane of glial cells. These allow the passage of several neuro- and gliotransmitters that may, combined with downstream paracrine signaling, complement direct GJ communication among glial cells and sustain glial-neuronal signaling. Mutations in the GJA1 gene encoding Cx43 have been identified in a rare, mostly autosomal dominant syndrome called oculodentodigital dysplasia (ODDD). ODDD patients display a pleiotropic phenotype reflected by eye, hand, teeth, and foot abnormalities, as well as craniofacial and bone malformations. Remarkably, neurological symptoms such as dysarthria, neurogenic bladder (manifested as urinary incontinence), spasticity or muscle weakness, ataxia, and epilepsy are other prominent features observed in ODDD patients. Over 10 mutations detected in patients diagnosed with neurological disorders are associated with altered functionality of Cx43 GJs/hemichannels, but the link between ODDD-related abnormal channel activities and neurologic phenotype is still elusive. Here, we present an overview on the nature of the mutants conveying structural and functional changes of Cx43 channels and discuss available evidence for aberrant Cx43 GJ and hemichannel function. In a final step, we examine the possibilities of how channel dysfunction may lead to some of the neurological manifestations of ODDD.

show abstract

“…Other mutations reported earlier in this region include p.Trp25Cys (p.W26C) reported recently by Furuta et al (2012) (Stenson et al, 2014).…”

Section: Discussionmentioning

confidence: 79%

Missense and deletion mutations in GJA1 causing oculodentodigital dysplasia in two Indian families

Dwarakanathan

Bhat

et al. 2015

Clinical Dysmorphology

View full text Add to dashboard Cite

A Novel GJA1 Mutation in Oculodentodigital Dysplasia with Progressive Spastic Paraplegia and Sensory Deficits

Cited by 21 publications

References 28 publications

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family

Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?

Missense and deletion mutations in GJA1 causing oculodentodigital dysplasia in two Indian families

Contact Info

Product

Resources

About