• Biomedical Science Letters
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• v.12 no.4
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• pp.311-318
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• 2006

The GJB2 mutation is mostly recessive in non-syndromic hearing loss, but specific mutations display a dominant type and syndromic hearing impairment. Both U54K and R75Q mutations present a dominant type in pedigrees with associated skin disorders. The purpose of this study was to investigate whether two GJB2 mutations can exhibit a dominant-negative effect on the growth abrogation and the gap junctional intercellular communication capacity exerted by wild-type connexin 26. A specific mutant region of GJB2 showed a loss of gap junction activity and a dominant negative effect on wild-type GJB2. The two mutants exerted a dominant-negative effect on the GJIC capacity and have independently effected GJB2 regulated growth of Hela cells; however, they have no dominant-negative growth effect on wild-type GJB2. It is proposed that the different mechanisms of the dominant-negative effect on wild-type GJB2 involve cell growth and GJIC function. This study describes mutations found in Korean deaf patients and that are typical of other east Asian regions.

• Journal of Audiology & Otology
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• v.23 no.4
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• pp.175-180
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• 2019

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.

• Korean Journal of Audiology
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• v.23 no.4
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• pp.175-180
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• 2019

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.2
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• pp.113-121
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• 2007

Hearing loss is a common congenital disorder that is frequently associated with mutations in the Cx26 gene (GJB2). Recently, the mutation analysis of GJB2 has been used in a newborn screening test for the detection of hearing impairment. Population-based studies should be performed before the application of genetic testing for the identification of deaf newborns. In this study, 8 positions of GJB2 mutations-including 35delG, 167delT, 235delC, V27I, V37I, M34T, E114G, and I203T-were analyzed using PCR-direct sequencing in a total of 437 healthy Korean neonates. DNAs from dried blood spots were extracted using a commercial DNA extraction kit. The PCR-amplified products (783 bps) of the GJB2 gene were detected using 2% agarose gel electrophoresis and subjected to direct sequencing. The sequences were compared with those in the GenBank database by using the BLAST program. In this study, 5 GJB2 mutations -including V27I (79G>A), V37I (109G>A), E114G (341A>G), I203T (608T>C), and 235delC- were found. Of the 437 neonate samples, 301 subjects showed GJB2 mutations (68.9%, 301/437). The V27I mutation was found in 271 subjects and was the most frequent (62.0%, 271/437). The E114G, I203T and V37I mutations were shown in 146, 17 and 14 subjects, respectively. The 235delC mutation was found in 1 subject. The E114G mutation was frequently accompanied by the V27I mutation. V27I/E114G (97.2%, 143/147) was the most common double mutation and 3 subjects had the double mutation V27I/I203T. A triple mutation, V27I/E114G/I203T, was found in 1 subject. In conclusion, PCR-direct sequencing is a convenient tool for the rapid detection of GJB2 mutations and this data might provide information for the genetic counseling of the GJB2 gene.

• The Journal of Korean Medicine
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• v.31 no.4
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• pp.63-78
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• 2010

Objectives: This study was carried out to know the effects of Gwan-Jul-Bang-7 (hereafter referred to GJB-7) on the inhibition of arthritis induced by collagen on the mouse. Methods: To assess the effects of GJB-7 on mouse with arthritis induced by collagen II, we conducted several experiments such as analysis of cytotoxicity, hepatotoxicity, arthritis index, total cell number of draining lymph nodes and paw joints, value of immunocyte in PBMC (peripheral blood mononuclear cell), DLN (draining lymph node) and paw joint, measurement of cytokine and anti-collagen II, observation of the histological changes of joint. Results: 1. Cytotoxicity against HFC (human fibroblast cells) was not observed in any concentration and hepatotoxicity was not observed in the GJB-7 treated group. 2. The incidence of arthritis significantly decreased. 3. Total cell number of draining lymph nodes significantly increased and total cell number of paw joints significantly decreased. 4. The percentage of $CD8^+$ cells in PBMC (peripheral blood mononuclear cell) significantly increased. The percentage of $CD3^+/CD69^+$, and $CD3^+/CD49b^+$ cells in PBMC significantly decreased. 5. The percentage of $CD19^+,\;CD3^+$, and $CD4^+/CD25^+$ cells in DLN (draining lymph nodes) significantly increased. The percentage of $B220^+/CD23^+$ cells in DLN significantly decreased. 6. The percentage of $CD3^+,\;CD4^+$, and $CD11b^+/Gr-1^+$ cells in paw joints significantly decreased. 7. The production of TNF-$\alpha$, IL-6, and MCP-1 significantly decreased. 8. Anti-collagen II in serum significantly decreased. 9. With the hematoxylin and eosin stain, inflammation of joint decreased. Under Masson's trichrome stain, the cartilage destruction and synovial cell proliferation and the expression of collagen fibers decreased. Conclusions: Comparison of the results for this study showed that GJB-7 had immunomodulatory effects. So we expect that GJB-7 could be used as an effective drug for not only rheumatoid arthritis but also another auto-immune diseases.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.107-109
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• 2018

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is caused by the mutation in GJB1 gene, characterized by the transient central nervous system involvement and long standing peripheral polyneuropathy which does not fulfill the criteria of demyelination or axonopathy. We describe a 37-year-old man with progressive bilateral leg weakness since his early teen. He suffered transient right hemiparesis, followed by quadriparesis at 14 years of age. When we examined him at 37 years of age, he presented a distal muscle weakness on lower extremities with a sensory symptom. The nerve conduction study demonstrated a motor conduction velocity between 26 and 49 m/s. The whole exome sequencing revealed a novel variant c.136 G>A in GJB1. This report will raise awareness in this rare disease, which is frequently misdiagnosed early in its course.

• Journal of Audiology & Otology
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• v.23 no.1
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• pp.20-26
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• 2019

Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. Subjects and Methods: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). Results: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.

• Korean Journal of Audiology
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• v.23 no.1
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• pp.20-26
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• 2019

Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. Subjects and Methods: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). Results: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.

• Annals of Clinical Neurophysiology
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• v.23 no.2
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• pp.130-133
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• 2021

X-linked Charcot Marie Tooth disease type 1 (CMTX1) is a clinically heterogenous X-linked hereditary neuropathy caused by mutation of the gene encoding gap junction beta 1 protein (GJB1). Typical clinical manifestations of CMTX1 are progressive weakness or sensory disturbance due to peripheral neuropathy. However, there have been some CMTX1 cases with accompanying central nervous system (CNS) manifestations. We report the case of a genetically confirmed CMTX1 patient who presented recurrent transient CNS symptoms without any symptom or sign of peripheral nervous system involvement.

• Steel and Composite Structures
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• v.8 no.2
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• pp.115-128
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• 2008

A method is proposed to estimate the ultimate strength of rectangular concrete-filled steel tubular (CFT) stub columns under axial compression. The ultimate strength of concrete core is determined by using the conception of the effective lateral confining pressure and a failure criterion of concrete under true triaxial compression, which takes into account the difference between the lateral confining pressure provided by the broad faces of the steel tube and that provided by the narrow faces of the steel tube. The longitudinal steel strength of broad faces and that of the narrow faces of the steel tube are calculated respectively due to that buckling tends to occur earlier and more extensively on the broader faces. Finally, the proposed method is verified with experimental results. Corresponding values of ultimate strength calculated by ACI (2005), AISC (1999) and GJB4142-2000 are given respectively for comparison. It is found from comparison that the proposed method shows a good agreement with the experimental results.