Laporte J, Hu L J, Kretz C, Mandel J L, Kioschis P, Coy J F, Klauck S M, Poustka A, Dahl N
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/U LP, B.P. 163, C.U. de Strasbourg, France.
Nat Genet. 1996 Jun;13(2):175-82. doi: 10.1038/ng0696-175.
X-linked recessive myotubular myopathy (MTM1) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. We have restricted the candidate region to 280 kb and characterized two candidate genes using positional cloning strategies. The presence of frameshift or missense mutations (of which two are new mutations) in seven patients proved that one of these genes is indeed implicated in MTM1. The protein encoded by the MTM1 gene is highly conserved in yeast, which is surprising for a muscle specific disease. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. At least three other genes, one located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man.
X连锁隐性肌管性肌病（MTM1）的特征是严重肌张力减退和全身肌肉无力，伴有肌纤维成熟障碍。我们已将候选区域限定在280 kb，并使用定位克隆策略对两个候选基因进行了特征分析。7名患者中存在移码或错义突变（其中两个是新突变），这证明这些基因之一确实与MTM1有关。MTM1基因编码的蛋白质在酵母中高度保守，这对于一种肌肉特异性疾病来说是令人惊讶的。该蛋白质包含酪氨酸磷酸酶活性位点的共有序列，酪氨酸磷酸酶是一大类参与信号转导的蛋白质。至少还有其他三个基因，其中一个位于距MTM1基因远端100 kb以内，它们编码的蛋白质具有非常高的序列相似性，并与MTM1基因一起定义了人类一个新的假定酪氨酸磷酸酶家族。
