MUTATIONS IN THE CONNEXIN-32 GENE IN X-LINKED DOMINANT CHARCOT-MARIE-TOOTH DISEASE (CMTX1)
MUTATIONS IN THE CONNEXIN-32 GENE IN X-LINKED DOMINANT CHARCOT-MARIE-TOOTH DISEASE (CMTX1)
复制标题
DOI：
10.1093/hmg/3.1.29
复制
发表时间：
1994-01-01
影响因子：
3.5
通讯作者：
HAITES, NE
中科院分区：
文献类型：
--
作者：
FAIRWEATHER, N;BELL, C;HAITES, NE
X连锁显性腓骨肌萎缩症（CMTX 1）是一种定位于Xq 13的周围神经病变，两侧为DXS 106（Xq11.2-q12）和DXS 559（Xq13.1）基因座。在这个大约2- 3 Mb的DNA区间内包含基因，连接蛋白32（基因座命名为GJ β 1）。该基因编码一种间隙连接蛋白，该蛋白在肝脏内和整个一系列其他肝脏组织中大量表达。我们对9个CMTX 1家族中受影响的个体的该基因外显子2的编码区进行了测序，并在其中8个家族中发现了与疾病分离的突变。检测到的突变包括密码子15、60、63、208和215处的错义点突变，密码子220处的无义点突变，密码子72/3中的一个碱基缺失，产生下游12个密码子的终止密码子，以及可以预测导致单个氨基酸丢失的三个碱基对缺失。这些发现与疾病CMTX 1是影响基因连接蛋白32（Cx 32）的突变的结果一致。
X-linked dominant Charcot-Marie-Tooth disease (CMTX1) is a peripheral neuropathy which maps to Xq13 and is flanked by the loci DXS106 (Xq11.2-q12) and DXS559 (Xq13.1). Contained within this interval of approximately 2-3Mb of DNA is the gene, connexin 32 (locus designation GJ beta 1). This gene encodes a gap junction protein which is expressed in large quantities within the liver and throughout a range of other mammmalian tissues. We have sequenced the coding region of exon 2 of this gene from affected individuals in nine families with CMTX 1 and have found mutations which segregate with the disease in eight of these families. The mutations detected include missense point mutations at codons 15, 60, 63, 208, and 215, a nonsense point mutation at codon 220, deletions of one base in codon 72/3 producing a stop codon 12 codons down stream and a three base pair deletion which can be predicted to result in the loss of a single amino acid. These findings are consistent with the disease CMTX1 being the result of mutations affecting the gene connexin 32 (Cx32).