Mutations in the 5′ region of the myotubularin-related protein 2 (MTMR2) gene in autosomal recessive hereditary neuropathy with focally folded myelin
Mutations in the 5′ region of the myotubularin-related protein 2 (MTMR2) gene in autosomal recessive hereditary neuropathy with focally folded myelin
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DOI：
10.1093/brain/124.5.907
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发表时间：
2001-05-01
期刊：
影响因子：
14.5
通讯作者：
Reilly, MM
中科院分区：
文献类型：
--
作者：
Houlden, H;King, RHM;Reilly, MM
局灶性折叠髓鞘已被认为是一个独特的特点，在一些严重的遗传性脱髓鞘神经病，在儿童期发病。这种情况已被证明是遗传异质性。染色体11q22上的肌微管蛋白相关蛋白2（MTMR 2）基因的改变最近被证明会引起这种表型。在4个不相关的家族中，MTMR 2基因的3'区域已经鉴定出突变，其中2个家族中的疾病已经通过遗传连锁分析定位到染色体11q22。我们对8个早发性常染色体隐性遗传性神经病家族的MTMR2基因的整个编码区和侧翼内含子区进行了测序。在一个英国人和一个印度人的MTMR 2基因5'端的第4外显子中发现了两个新的突变。在这两个家庭的临床表型和腓肠神经病理的严重程度不同，与先证者在英国家庭有一个更早的发病和更严重的神经病变与突出的颅神经受累。这可能是由于突变类型和小核苷酸多态性可能参与表型调节。详细的腓肠神经病理在这两个案件。MTMR 2基因突变是常染色体隐性脱髓鞘性神经病的重要原因，进一步鉴定突变并确定其表型将有助于阐明这组疾病的遗传分类。
Focally folded myelin has been recognized as a distinctive feature in some individuals with severe inherited demyelinating neuropathy, with an onset in childhood. Such cases have been shown to be genetically heterogeneous. Alterations in the myotubularin-related protein 2 (MTMR2) gene on chromosome 11q22 have recently been shown to give rise to this phenotype. Mutations have been identified in the 3' region of the MTMR2 gene in four unrelated families, in two of whom the disorder had been mapped to chromosome 11q22 by genetic linkage analysis. We have sequenced the entire coding region and flanking intronic regions of the MTMR2 gene in eight families with early onset autosomal recessive neuropathies. Two novel mutations were identified in exon 4 at the 5' end of the MTMR2 gene in an English and an Indian family. The clinical phenotype and sural nerve pathology in these two families differs in severity, with the proband in the English family having an earlier onset and more severe neuropathy with prominent cranial nerve involvement. This is probably due to mutation type and possible involvement of small nucleotide polymorphisms in phenotype modulation. Detailed sural nerve pathology is presented in both cases. Mutations in the MTMR2 gene are thus an important cause of autosomal recessive demyelinating neuropathy, Identifying further mutations and defining their phenotype will help to clarify the genetic classification of this group of disorders.