Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression.
Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression.
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DOI：
10.1186/1750-1172-8-173
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发表时间：
2013-10-28
影响因子：
3.7
通讯作者：
Anheim M
中科院分区：
文献类型：
--
作者：
Mignot C;Apartis E;Durr A;Marques Lourenço C;Charles P;Devos D;Moreau C;de Lonlay P;Drouot N;Burglen L;Kempf N;Nourisson E;Chantot-Bastaraud S;Lebre AS;Rio M;Chaix Y;Bieth E;Roze E;Bonnet I;Canaple S;Rastel C;Brice A;Rötig A;Desguerre I;Tranchant C;Koenig M;Anheim M
常染色体隐性小脑共济失调 2 (ARCA2) 是最近发现的一种隐性共济失调，由泛醌缺乏和 ADCK3 基因双等位基因突变所致。全球报告的 21 名患者的表型差异很大。因此，在没有泛醌缺乏证据的情况下，很难确定哪些共济失调患者适合进行 ADCK3 筛查。我们在这里报告了来自7个家庭的10名新诊断患者的临床和分子数据，并更新了之前文章中报道的另外4名患者的病史，以描绘ARCA2表型的临床谱并为分子诊断提供指导。所有 14 名患者的最初症状均出现在成年之前。所有病例均出现小脑萎缩。共济失调的进行性和严重程度差异很大，但没有患者出现典型的不可抗拒的共济失调病程，而这种病程是其他儿童期发病的隐性共济失调的特征。共济失调经常与其他神经系统症状相关。重要的是，中风样发作导致两名患者的神经状态显着恶化。辅酶Q10治疗显着改善了另外两名患者的运动障碍，包括共济失调。在10名新患者中发现的7个新的ADCK3突变是两个错义突变和五个截短突变。基因型和表型之间没有明显的相关性。我们的系列揭示了 ARCA2 的临床谱涵盖一系列共济失调表型。一方面，它可能表现为进展非常缓慢的纯粹共济失调，另一方面，表现为伴有小脑萎缩的严重婴儿脑病。然而，大多数患者的表型介于两者之间。其特征是与中枢神经系统受累的其他体征相关的非常缓慢进展或明显稳定的共济失调。我们建议对具有这种表型的患者以及患有小脑萎缩和中风样发作的患者进行 ADCK3 的分子分析。具有严重 ARCA2 表型的患者的诊断也可以根据生物学数据进行，即低泛醌水平或泛醌缺乏的功能证据。这一诊断至关重要，因为一些患者的神经系统状态可能会通过泛醌治疗得到改善。
Autosomal recessive cerebellar ataxia 2 (ARCA2) is a recently identified recessive ataxia due to ubiquinone deficiency and biallelic mutations in the ADCK3 gene. The phenotype of the twenty-one patients reported worldwide varies greatly. Thus, it is difficult to decide which ataxic patients are good candidates for ADCK3 screening without evidence of ubiquinone deficiency. We report here the clinical and molecular data of 10 newly diagnosed patients from seven families and update the disease history of four additional patients reported in previous articles to delineate the clinical spectrum of ARCA2 phenotype and to provide a guide to the molecular diagnosis. First signs occurred before adulthood in all 14 patients. Cerebellar atrophy appeared in all instances. The progressivity and severity of ataxia varied greatly, but no patients had the typical inexorable ataxic course that characterizes other childhood-onset recessive ataxias. The ataxia was frequently associated with other neurological signs. Importantly, stroke-like episodes contributed to significant deterioration of the neurological status in two patients. Ubidecarenone therapy markedly improved the movement disorders, including ataxia, in two other patients. The 7 novel ADCK3 mutations found in the 10 new patients were two missense and five truncating mutations. There was no apparent correlation between the genotype and the phenotype. Our series reveals that the clinical spectrum of ARCA2 encompasses a range of ataxic phenotypes. On one end, it may manifest as a pure ataxia with very slow progressivity and, on the other end, as a severe infantile encephalopathy with cerebellar atrophy. The phenotype of most patients, however, lies in between. It is characterized by a very slowly progressive or apparently stable ataxia associated with other signs of central nervous system involvement. We suggest undergoing the molecular analysis of ADCK3 in patients with this phenotype and in those with cerebellar atrophy and a stroke-like episode. The diagnosis of patients with a severe ARCA2 phenotype may also be performed on the basis of biological data, i.e. low ubiquinone level or functional evidence of ubiquinone deficiency. This diagnosis is crucial since the neurological status of some patients may be improved by ubiquinone therapy.
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影响因子：
13.6
作者：
Diomedi-Camassei, Francesca;Di Giandomenico, Silvia;Emma, Francesco
通讯作者：
Emma, Francesco
影响因子：
3.9
作者：
Hennekam, Raoul C. M.;Biesecker, Leslie G.
通讯作者：
Biesecker, Leslie G.
影响因子：
9.8
作者：
Mollet, Julie;Delahodde, Agnes;Roetig, Agnes
通讯作者：
Roetig, Agnes
影响因子：
3.1
作者：
Terracciano, Alessandra;Renaldo, Florence;Zanni, Ginevra;D'Amico, Adele;Pastore, Anna;Barresi, Sabina;Valente, Enza Maria;Piemonte, Fiorella;Tozzi, Giulia;Carrozzo, Rosalba;Valeriani, Massimiliano;Boldrini, Renata;Mercuri, Eugenio;Santorelli, Filippo Maria;Bertini, Enrico
通讯作者：
Bertini, Enrico
影响因子：
14.5
作者：
Anheim, M.;Monga, B.;Koenig, M.
通讯作者：
Koenig, M.