Leucine-485 deletion variant of BRAF may exhibit the severe end of the clinical spectrum of CFC syndrome
Leucine-485 deletion variant of BRAF may exhibit the severe end of the clinical spectrum of CFC syndrome
复制标题
DOI：
10.1038/s10038-019-0579-3
复制
发表时间：
2019-05-01
影响因子：
3.5
通讯作者：
Haginoya, Kazuhiro
中科院分区：
文献类型：
--
作者：
Suzuki-Muromoto, Sato;Miyabayashi, Takuya;Haginoya, Kazuhiro
心面部皮肤综合征患者BRAF变异的基因-表型相关性尚不明确。在这里，我们报告一例严重的临床表型和一个新的BRAF变异体，P.Leu485del。本病例表现为严重的智力障碍、意识障碍、多动症、不自主运动、早发性难治性癫痫发作、脑部磁共振成像的髓鞘形成延迟，以及多囊和发育不良的肾脏，这些都是与BRAF变异型相关的CFC或RAS/丝裂原活化蛋白激酶综合征中以前未见报道的异常。发育性脑病、癫痫性脑病和智力亢进患者的鉴别诊断中应包括由BRAF变异引起的CFC综合征。此外，我们需要记住，错义变异或亮氨酸-485的缺失可能与严重症状有关。
The genotype-phenotype correlation in BRAF variant in cardio-facio-cutaneous (CFC) syndrome is not clearly defined. Here we report a case with a severe clinical phenotype and a novel BRAF variant, p.Leu485del. The present case showed severe intellectual disability, impaired awareness, hyperekplexia, involuntary movements, early onset refractory seizures, and delayed myelination on brain magnetic resonance imaging as well as a polycystic and dysplastic kidney, which are previously unreported anomalies in CFC or RAS/mitogen-activated protein kinase syndromes related to BRAF variant. CFC syndrome, especially caused by BRAF variant, should be included in the differential diagnosis of patients with developmental and epileptic encephalopathies and hyperekplexia. Furthermore, we need to keep in mind that missense variants or the deletion of Leucine-485 may be associated with severe symptoms.