Defining the phenotypical spectrum associated with variants in TUBB2A.
Defining the phenotypical spectrum associated with variants in TUBB2A.
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DOI：
10.1136/jmedgenet-2019-106740
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发表时间：
2021-01
影响因子：
4
通讯作者：
Stouffs K
中科院分区：
文献类型：
--
作者：
Brock S;Vanderhasselt T;Vermaning S;Keymolen K;Régal L;Romaniello R;Wieczorek D;Storm TM;Schaeferhoff K;Hehr U;Kuechler A;Krägeloh-Mann I;Haack TB;Kasteleijn E;Schot R;Mancini GMS;Webster R;Mohammad S;Leventer RJ;Mirzaa G;Dobyns WB;Bahi-Buisson N;Meuwissen M;Jansen AC;Stouffs K
属于微管蛋白超家族的基因变异导致了被称为微管蛋白病的脑畸形的异质谱。TUBB 2A的变体已在10名患者中报告，这些患者具有广泛的脑成像特征，范围从正常皮质到多小脑回，而1名患者报告了小脑蚓部的进行性萎缩。为了进一步完善与TUBB 2A相关的表型谱，对通过作者的国际网络招募的12例具有致病性TUBB 2A变体的患者的临床和影像学特征进行了审查。我们报告了12例患者，其中8例新变异和1例复发变异遍布TUBB 2A基因，但编码蛋白质表面的氨基酸簇。11例患者（91.7%）在生命早期发生癫痫发作。所有患者均患有智力残疾，11例患者有严重的运动发育迟缓，其中4例患者（36.4%）无法行走。5名患者的大脑皮层正常，7名患者表现出不同严重程度的脑回障碍。与其他微管蛋白病相比，TUBB 2A患者中相关脑畸形的发生率较低。所有患者均无进行性小脑萎缩。与TUBB 2A致病性变体相关的成像表型是高度可变的，范围从正常皮质到广泛的脑回障碍伴相关脑畸形。对于复发性变异，没有明确的基因型-表型相关性可以建立，这表明额外的修饰剂的作用。
Variants in genes belonging to the tubulin superfamily account for a heterogeneous spectrum of brain malformations referred to as tubulinopathies. Variants in TUBB2A have been reported in 10 patients with a broad spectrum of brain imaging features, ranging from a normal cortex to polymicrogyria, while one patient has been reported with progressive atrophy of the cerebellar vermis. In order to further refine the phenotypical spectrum associated with TUBB2A, clinical and imaging features of 12 patients with pathogenic TUBB2A variants, recruited via the international network of the authors, were reviewed. We report 12 patients with eight novel and one recurrent variants spread throughout the TUBB2A gene but encoding for amino acids clustering at the protein surface. Eleven patients (91.7%) developed seizures in early life. All patients suffered from intellectual disability, and 11 patients had severe motor developmental delay, with 4 patients (36.4 %) being non-ambulatory. The cerebral cortex was normal in five individuals and showed dysgyria of variable severity in seven patients. Associated brain malformations were less frequent in TUBB2A patients compared with other tubulinopathies. None of the patients had progressive cerebellar atrophy. The imaging phenotype associated with pathogenic variants in TUBB2A is highly variable, ranging from a normal cortex to extensive dysgyria with associated brain malformations. For recurrent variants, no clear genotype–phenotype correlations could be established, suggesting the role of additional modifiers.
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影响因子：
--
作者：
Mukhtar T;Taylor V
通讯作者：
Taylor V
影响因子：
7.1
作者：
Fallet-Bianco C;Laquerrière A;Poirier K;Razavi F;Guimiot F;Dias P;Loeuillet L;Lascelles K;Beldjord C;Carion N;Toussaint A;Revencu N;Addor MC;Lhermitte B;Gonzales M;Martinovich J;Bessieres B;Marcy-Bonnière M;Jossic F;Marcorelles P;Loget P;Chelly J;Bahi-Buisson N
通讯作者：
Bahi-Buisson N
影响因子：
3.5
作者：
Sferra, Antonella;Fattori, Fabiana;Bertini, Enrico
通讯作者：
Bertini, Enrico
影响因子：
2.9
作者：
Leandro-Garcia, Luis J.;Leskelae, Susanna;Rodriguez-Antona, Cristina
通讯作者：
Rodriguez-Antona, Cristina
影响因子：
14.9
作者：
Waterhouse A;Bertoni M;Bienert S;Studer G;Tauriello G;Gumienny R;Heer FT;de Beer TAP;Rempfer C;Bordoli L;Lepore R;Schwede T
通讯作者：
Schwede T