Two novel mutations in the GDAP and PRX genes in early onset Charcot-Marie-Tooth syndrome
Two novel mutations in the GDAP and PRX genes in early onset Charcot-Marie-Tooth syndrome
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DOI：
10.1055/s-2008-1077085
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发表时间：
2008-02-01
期刊：
影响因子：
1.4
通讯作者：
Janecke, A. R.
中科院分区：
文献类型：
--
作者：
Auer-Grumbach, M.;Fischer, C.;Janecke, A. R.
常染色体隐性遗传性Charcot-Marie-Tooth综合征(AR-CMT)通常以婴儿发病和严重表型为特征。神经节苷脂诱导分化相关蛋白1(GDAP1)基因突变被认为是AR-CMT的常见原因。外周轴蛋白(Prx)基因突变很少见。它们与周围神经的严重脱髓鞘有关，有时会导致明显的感觉障碍。为了评估GDAP1和PRX突变在早发性CMT中的频率，我们检查了7个AR-CMT家系和12名散发性CMT患者，他们都表现为进行性远端肌肉无力和消瘦。在一个家庭中，明显的感觉异常和感觉性共济失调从儿童早期就很明显。我们在三个家系中检测到四个GDAP1突变(L58LfsX4、R191X、L239F和P153L)，其中一个是新发现的，被预测会导致蛋白质功能丧失。在另外一个有明显感觉异常的家庭中，发现了一种新的纯合子Prx突变(A700PfsX17)。12例散发性病例均未发现突变。这项研究表明，GDAP1基因突变是早发性AR-CMT的常见原因。在早发性脱髓鞘AR-CMT和严重感觉丧失的患者中，Prx是要检测的基因之一。
Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. in three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested.