Refining the phenotype of α-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly
Refining the phenotype of α-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly
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DOI：
10.1111/j.1399-0004.2008.01093.x
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发表时间：
2008-11-01
影响因子：
3.5
通讯作者：
Uyanik, G.
中科院分区：
文献类型：
--
作者：
Morris-Rosendahl, D. J.;Najm, J.;Uyanik, G.
最近发现α-1a微管蛋白(TUBA1A)基因突变导致皮质畸形，类似于经典的无脑畸形，但具有特定的特征组合。到目前为止，已经在5名患者和3名胎儿中描述了TUBA1A突变。我们的目的是确定TUBA1A突变在无脑畸形患者中有多常见，并有助于确定与TUBA1A突变相关的表型。我们对46例经典型无脑畸形患者进行了TUBA1A基因突变分析。在44名患者中，之前排除了Lis1和/或DCX基因的突变；在2名患者中，仅根据磁共振成像(MRI)结果进行了TUBA1A的突变分析。我们在五名在脑MRI上有不同类型的无脑畸形的患者中发现了三个新的突变和一个重复突变。5例患者中有4例为先天性小头畸形，均有胼胝体发育不全和小脑发育不全，以及不同的皮质畸形，包括微妙的皮质下带异位和内囊前肢缺失或发育不全。我们估计TUBA1A基因突变在经典型无脑畸形患者中的频率约为4%，尽管不像LIS1或DCX基因突变那样常见，但TUBA1A基因突变分析应包括在经典型无脑畸形的分子遗传学诊断中，特别是在具有本文所强调的特征组合的患者中。
Mutations in the alpha-1a Tubulin (TUBA1A) gene have recently been found to cause cortical malformations resemblant of classical lissencephaly but with a specific combination of features. To date, TUBA1A mutations have been described in five patients and three foetuses. Our aims were to establish how common TUBA1A mutations are in patients with lissencephaly and to contribute to defining the phenotype associated with TUBA1A mutation. We performed mutation analysis in the TUBA1A gene in 46 patients with classical lissencephaly. In 44 of the patients, mutations in the LIS1 and/or DCX genes had previously been excluded; in 2 patients, mutation analysis was only performed in TUBA1A based on magnetic resonance imaging (MRI) findings. We identified three new mutations and one recurrent mutation in five patients with variable patterns of lissencephaly on brain MRI. Four of the five patients had congenital microcephaly, and all had dysgenesis of the corpus callosum and cerebellar hypoplasia, and variable cortical malformations, including subtle subcortical band heterotopia and absence or hypoplasia of the anterior limb of the internal capsule. We estimate the frequency of mutation in TUBA1A gene in patients with classical lissencephaly to be approximately 4%, and although not as common as mutations in the LIS1 or DCX genes, mutation analysis in TUBA1A should be included in the molecular genetic diagnosis of classical lissencephaly, particularly in patients with the combination of features highlighted in this paper.