Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome

Abstract

Summary Background Germline missense mutations in the GJB2 gene that encodes connexin‐26 (Cx26) have recently been found to be the cause of the keratitis–ichthyosis–deafness (KID) syndrome. Objectives To define the GJB2 mutations in three Japanese patients with KID syndrome. Methods Genomic DNA was extracted from peripheral blood and used to amplify the GJB2 gene. Direct sequencing and endonuclease digestion were used for mutation analysis and DNA‐based diagnosis. Results We identified two heterozygous mis‐sense mutations (D50Y, D50N) in the GJB2 gene in three Japanese patients with KID syndrome. All mutations were located on the first extracellular domain of Cx26. Conclusions These data expand the GJB2 mutation database and show that a dominant mutation of Cx26 can cause KID syndrome in Japanese patients.

Uso do bevacizumab (Avastin®) na síndrome KID: relato de caso

“…Mutações no gene GJB2 que codifica a conexina 26 -componente das "gap junctions" das células epiteliais -recentemente têm sido descritas em pacientes com síndrome KID. Embora a distribuição da conexina 26 na córnea ainda não esteja bem definida, disfunções nas "gap junctions" do epitélio corneano podem ser responsáveis por alterações da superfície ocular (10)(11)(12) . O tratamento ocular na síndrome KID é sintomático, não havendo ainda descrição de drogas ou tratamento cirúrgico que possam modificar o curso e prognóstico dessa doença.…”

In Silico Study of Human Gap Junction Beta-2 Protein by Homology Modeling

“…The CB1-CG1 bond rotation affects the angle (105.45 o for wild-type to 111.17 o for mutant) and the decrease in the force field energy of the protein from 6946.490 kJ/mol to 6811.053 kJ/mol ( Table 2). The substitution of the conserved residue aspartic acid 50 by asparagine (Asp50Asn) in the first extracellular domain of connexin 26 causes Keratitis-Ichthyosis-Deafness Syndrome (Yotsumoto et al, 2003). This mutation is likely to be the factor that disturbs the communication of ions, metabolites, and signaling molecules in neighboring cells and affects homeostasis by disturbing the bonding and energies (Saez et al, 2000).…”

“…About 20 mutations of gap junction β-2 have been described as being related to diseases (Abe et al, 2000) and various syndromes, such as Bart-Pumphrey Syndrome, KeratitisIchthyosis-Deafness Syndrome, and Vohwinkel Syndrome. (Richard et al, 2004;Snoeckx et al, 2005;Yotsumoto et al, 2003). The mutations alter the amino acid sequence of connexin 26 and result in impaired functioning of the protein associated with ion channels, especially.…”

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

“…Heterozygous missense mutations in GJB2 were found in several conditions associating deafness and hyperkeratosis: D66H in mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome, OMIM 124500) [Maestrini et al, 2002], G59A and R75Q in palmoplantar hyperkeratosis with deafness (PPKD, OMIM 148350) [Heathcote et al, 2000;Uyguner et al, 2002], as well as D50Y and D50N in keratitisichthyosis-deafness syndrome (KID, OMIM 148210), and in hystrix like-ichthyosis-deafness syndrome (HID, OMIM 602540) [Richard et al, 2002;van Geel et al, 2002;Yotsumoto et al, 2003]. Richard et al [2002] also described two sporadic cases of KID syndrome with G12R and S17F missense mutations, each patient showing a different mutation.…”