Kioschis P, Wiemann S, Heiss N S, Francis F, Götz C, Poustka A, Taudien S, Platzer M, Wiehe T, Beckmann G, Weber J, Nordsiek G, Rosenthal A
Deutsches Krebsforschungszentrum, Molekulare Genomanalyse, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.
Genomics. 1998 Dec 1;54(2):256-66. doi: 10.1006/geno.1998.5560.
MTM1 is responsible for X-linked recessive myotubular myopathy, which is a congenital muscle disorder linked to Xq28. MTM1 is highly conserved from yeast to humans. A number of related genes also exist. The MTM1 gene family contains a consensus sequence consisting of the active enzyme site of protein tyrosine phosphatases (PTPs), suggesting that they belong to a new family of PTPs. Database searches revealed homology of myotubularin and all related peptides to the cisplatin resistance-associated alpha protein, which implicates an as yet unknown function. In addition, homology to the Sbf1 protein (SET binding factor 1), involved in the oncogenic transformation of fibroblasts and differentiation of myoblasts, was also evident. We describe 225 kb of genomic sequence containing MTM1 and the related gene, MTMR1, which lies 20 kb distal to MTM1. Although there is only moderate conservation of the exons, the striking similarity in the gene structures indicates that these two genes arose by duplication. Calculations suggest that this event occurred early in evolution long before separation of the human and mouse lineages. So far, mutations have been identified in the coding sequence of only 65% of the patients analyzed, indicating that the remaining mutations may lie in noncoding regions of MTM1 or possibly in MTMR1. Knowledge of the genomic sequence will facilitate mutation analyses of the coding and noncoding sequences of MTM1 and MTMR1.
MTM1 基因与 X 连锁隐性肌管性肌病相关，这是一种与 Xq28 相关的先天性肌肉疾病。MTM1 基因从酵母到人类高度保守。还存在许多相关基因。MTM1 基因家族包含一个由蛋白酪氨酸磷酸酶（PTP）的活性酶位点组成的共有序列，这表明它们属于一个新的 PTP 家族。数据库搜索显示，肌管素及所有相关肽与顺铂耐药相关的α蛋白具有同源性，这暗示了一种未知的功能。此外，与参与成纤维细胞致癌转化和肌成纤维细胞分化的 Sbf1 蛋白（SET 结合因子 1）也有明显的同源性。我们描述了包含 MTM1 和相关基因 MTMR1 的 225 kb 基因组序列，MTMR1 位于 MTM1 下游 20 kb 处。尽管外显子只有适度的保守性，但基因结构的显著相似性表明这两个基因是通过复制产生的。计算表明，这一事件发生在进化早期，远早于人类和小鼠谱系的分离。到目前为止，在仅 65% 的分析患者的编码序列中发现了突变，这表明其余突变可能位于 MTM1 的非编码区或可能在 MTMR1 中。对基因组序列的了解将有助于对 MTM1 和 MTMR1 的编码和非编码序列进行突变分析。
