Novel variant in CADM3 causes Charcot-Marie-Tooth disease.
Novel variant in CADM3 causes Charcot-Marie-Tooth disease.
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DOI：
10.1093/braincomms/fcad227
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
最近有报道称，CADM 3在三个独立的高加索家族中引起了一种罕见的轴突型腓骨肌萎缩症，该家族具有复发性改变。我们描述了第一个选择性致病突变CADM 3在一个家庭从非洲黑人，也观察到从头在患者的高加索血统。该疾病的遗传分别符合常染色体显性和散发模式。8名患者及其亲属从两个家庭中招募。平均诊断年龄为33.9岁，行走困难通常是首发症状。神经系统检查显示远端肌肉无力和萎缩，感觉丧失和手足畸形。注意到高临床变异性，但如在CADM 3相关神经病变中所见，一些患者的手臂症状更明显。神经传导研究显示，在大多数检查的神经中没有反应，并且记录了轴突型神经病。全外显子组测序揭示了CADM 3中一种新型错义变体（c.1102G>T; Gly 368 Cys），与疾病分离。功能分析表明，在CADM 3-Gly 368 Cys蛋白水平的膜和其预测的二级结构的主要结构变化显着下降。因此，我们扩展了CADM 3的基因型谱，强调了在非洲等代表性不足的人群中进行遗传研究的必要性。Yalcouyé等人报道CADM 3基因的变异导致轴突型神经病。这项研究提供了CADM 3在腓骨肌萎缩症发病机制中的作用的进一步证据，并提出了在遗传研究中包括非洲人等多样化和代表性不足的人群的重要性。
CADM3 has been recently reported causing a rare axonal Charcot–Marie–Tooth disease in three independent Caucasian families carrying a recurrent change. We describe the first alternative causative mutation in CADM3 in a family from black African and also observed de novo in a patient of Caucasian ancestry. The disease inheritance was consistent with autosomal dominant and sporadic patterns, respectively. Eight patients and their relatives were enroled from both families. The mean age at diagnosis was 33.9 years, and walking difficulty was commonly the first symptom. Neurological examination showed distal muscle weakness and atrophy, sensory loss and foot and hand deformities. A high clinical variability was noted, but as seen in CADM3-associated neuropathy, symptoms were more pronounced in the arms in some patients. Nerve conduction studies showed no response in most of the examined nerves, and an axonal type of neuropathy, where recorded. Whole exome sequencing revealed a novel missense variant (c.1102G>T; Gly368Cys) in CADM3, segregating with the disease. Functional analyses showed a significant decrease in CADM3-Gly368Cys protein levels in the membrane and major structural changes in its predicted secondary structure. Therefore, we extend the genotype spectrum of CADM3, underlining the need for genetic studies in underrepresented populations like in Africa. Yalcouyé et al. report that variants in CADM3 gene cause an axonal-type neuropathy. This study provides further evidence of the implication of CADM3 in the pathogenesis of Charcot–Marie–Tooth disease and raises the importance of including diverse and underrepresented populations like African in genetic studies.
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影响因子：
2.2
作者：
Traore, M.;Landoure, G.;Fischbeck, K. H.
通讯作者：
Fischbeck, K. H.
全外显子组测序揭示了 2 型腓骨肌萎缩症更广泛的变异谱
影响因子：
2.2
作者：
Lin, Shan;Xu, Liu-Qing;He, Jin
通讯作者：
He, Jin
DOI：
10.1136/jnnp-2014-308826
发表时间：
2015-08
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Fridman V;Bundy B;Reilly MM;Pareyson D;Bacon C;Burns J;Day J;Feely S;Finkel RS;Grider T;Kirk CA;Herrmann DN;Laurá M;Li J;Lloyd T;Sumner CJ;Muntoni F;Piscosquito G;Ramchandren S;Shy R;Siskind CE;Yum SW;Moroni I;Pagliano E;Zuchner S;Scherer SS;Shy ME;Inherited Neuropathies Consortium
通讯作者：
Inherited Neuropathies Consortium
影响因子：
14.9
作者：
Heo L;Park H;Seok C
通讯作者：
Seok C
影响因子：
5.3
作者：
Guinto CO;Diarra S;Diallo S;Cissé L;Coulibaly T;Diallo SH;Taméga A;Chen KL;Schindler AB;Bagayoko K;Simaga A;Blackstone C;Fischbeck KH;Landouré G
通讯作者：
Landouré G