Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work conce...Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work concerns the functional expression of gap junction protein connexin 43 (Cx43) in normal human lung cells and the changes in lung carcinoma cells. By. using Northern blot hybridization analysis and Cx43 immunocytochemical methods, it was otherved that cultured normal human embryonic lung cells expressed a high level of Cx43 in both mRNA and protein levels.The Cx43 immunofluorescence was localized at cell membrane regions corresponding to the location of gap junctions. These normal lung cells were competent of intercellular communication function as detected by Lucifer yellow dye transfer. In contrast to normal celis, Cx43 mRNA and protein was not detectable in the carcinoma PG cell line. These tumor cells were defective of intercellular communication function. These results demonstrate that Cx43 is expressed in normal cultured human embryonic lung cells but not in lung tumor cells. The lack of intercellular communication in the lung tumor cell line correlates with dysfunctional intercellular communication. The suggestive role of Cx as a tumor suppersor gene is discussed.展开更多
Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approxi...Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.展开更多
Congenital cataract is a crystallin severe blinding disease and genetic factors in disease development are important. Crystallin growth is under a combination of genes and their products in time and space to complete ...Congenital cataract is a crystallin severe blinding disease and genetic factors in disease development are important. Crystallin growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Congenital cataract-related genes, included crystallin protein gene (CRYAA, CRYAB, CRYBA1/A3, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS), gap junction channel protein gene (GJA1, GJA3, GJA8), membrane protein gene (GJA3, GJA8, MIP, LIM2), cytoskeletal protein gene (BF-SP2), transcription factor genes (HSF4, MAF, PITX3, PAX6), ferritin light chain gene (FTL), fibroblast growth factor (FGF) and so on. Currently, there are about 39 genetic loci isolated to which primary cataracts have been mapped, although the number is constantly increasing and depends to some extent on definition. We summarized the recent advances on epidemiology and genetic locations of congenital cataract in this review.展开更多
Background： X-linked Charcot-Marie-Tooth type 1 （CMT1 X） disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein （GJB1） gene （also known as connexin...Background： X-linked Charcot-Marie-Tooth type 1 （CMT1 X） disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein （GJB1） gene （also known as connexin 32）. This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. Methods： A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJBI mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing （NGS）. Nucleotide alternations were confirnled with Sanger sequencing. Results： The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years （ranging from 1 year to 42 years）. The sudden onset of cerebral symptoms appeared in four patients （ 18.2%）： two were initial symptoms. One case had constant central nervous system （CNS） signs. There were 19 different heterozygous mutations, including 15 known mutations and tbur novel mutations （c. II5G〉T, c.380T〉A, c.263C〉A, and c.818_819insGGGCT）. Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 （TM1）, 4.5% in TM2, 27.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 （EC1）, 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-ternlinal domain. CMTIX with CNS impairment appeared in five （22.7%） of these patients. Conclusions： This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJBI gene were hotspot in Chinese CMT1X patients.展开更多
文摘Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work concerns the functional expression of gap junction protein connexin 43 (Cx43) in normal human lung cells and the changes in lung carcinoma cells. By. using Northern blot hybridization analysis and Cx43 immunocytochemical methods, it was otherved that cultured normal human embryonic lung cells expressed a high level of Cx43 in both mRNA and protein levels.The Cx43 immunofluorescence was localized at cell membrane regions corresponding to the location of gap junctions. These normal lung cells were competent of intercellular communication function as detected by Lucifer yellow dye transfer. In contrast to normal celis, Cx43 mRNA and protein was not detectable in the carcinoma PG cell line. These tumor cells were defective of intercellular communication function. These results demonstrate that Cx43 is expressed in normal cultured human embryonic lung cells but not in lung tumor cells. The lack of intercellular communication in the lung tumor cell line correlates with dysfunctional intercellular communication. The suggestive role of Cx as a tumor suppersor gene is discussed.
文摘Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.
文摘Congenital cataract is a crystallin severe blinding disease and genetic factors in disease development are important. Crystallin growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Congenital cataract-related genes, included crystallin protein gene (CRYAA, CRYAB, CRYBA1/A3, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS), gap junction channel protein gene (GJA1, GJA3, GJA8), membrane protein gene (GJA3, GJA8, MIP, LIM2), cytoskeletal protein gene (BF-SP2), transcription factor genes (HSF4, MAF, PITX3, PAX6), ferritin light chain gene (FTL), fibroblast growth factor (FGF) and so on. Currently, there are about 39 genetic loci isolated to which primary cataracts have been mapped, although the number is constantly increasing and depends to some extent on definition. We summarized the recent advances on epidemiology and genetic locations of congenital cataract in this review.
基金This study was supported by a grant from the National Science Foundation of China （No. 81471185）.
文摘Background： X-linked Charcot-Marie-Tooth type 1 （CMT1 X） disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein （GJB1） gene （also known as connexin 32）. This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. Methods： A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJBI mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing （NGS）. Nucleotide alternations were confirnled with Sanger sequencing. Results： The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years （ranging from 1 year to 42 years）. The sudden onset of cerebral symptoms appeared in four patients （ 18.2%）： two were initial symptoms. One case had constant central nervous system （CNS） signs. There were 19 different heterozygous mutations, including 15 known mutations and tbur novel mutations （c. II5G〉T, c.380T〉A, c.263C〉A, and c.818_819insGGGCT）. Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 （TM1）, 4.5% in TM2, 27.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 （EC1）, 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-ternlinal domain. CMTIX with CNS impairment appeared in five （22.7%） of these patients. Conclusions： This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJBI gene were hotspot in Chinese CMT1X patients.
