Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia
Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia
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DOI：
10.1086/346090
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发表时间：
2003-02-01
影响因子：
9.8
通讯作者：
Jabs, EW
中科院分区：
文献类型：
--
作者：
Paznekas, WA;Boyadjiev, SA;Jabs, EW
缝隙连接是细胞间通道的集合体，通过小离子和信号分子的交换调节各种生理和发育过程。这些通道由连接蛋白家族蛋白组成，其允许通道组成和电导性质的多样性。人类连接蛋白43基因，或GJA 1，位于人类染色体6 q22-q23的候选区域内的眼齿指发育不良基因座。这种常染色体显性遗传综合征表现为颅面（眼、鼻和牙齿）和肢体畸形、痉挛性截瘫和神经变性。III型并指畸形和传导性耳聋可在某些病例中发生，在罕见情况下观察到心脏异常。我们发现，在所有17个家庭的突变GJA 1基因与眼齿趾发育不良，我们筛选。检测到16个不同的错义突变和1个密码子重复。这些突变可能导致通道的错误组装或改变通道传导特性。其他地方报道的gja 1动物突变体的表达模式和表型特征与眼齿指发育不良的多效性临床表现相一致。
Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human connexin 43 gene, or GJA1, is located at human chromosome 6q22-q23 within the candidate region for the oculodentodigital dysplasia locus. This autosomal dominant syndrome presents with craniofacial (ocular, nasal, and dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Syndactyly type III and conductive deafness can occur in some cases, and cardiac abnormalities are observed in rare instances. We found mutations in the GJA1 gene in all 17 families with oculodentodigital dysplasia that we screened. Sixteen different missense mutations and one codon duplication were detected. These mutations may cause misassembly of channels or alter channel conduction properties. Expression patterns and phenotypic features of gja1 animal mutants, reported elsewhere, are compatible with the pleiotropic clinical presentation of oculodentodigital dysplasia.