PT -期刊文章盟Jose-Alberto帕尔马AU -大地高盟苏珊Slaugenhaupt AU -露西Norcliffe-Kaufmann盟霍雷肖Kaufmann TI -扩大先天性感官和自主神经病变的基因谱全外显子组测序(N3.002) DP - 2018年4月10 TA -神经病学PG - N3.002 VI - 90 IP - 15补充4099 - //www.ez-admanager.com/content/90/15_Supplement/N3.002.short 4100 - //www.ez-admanager.com/conten首页t/90/15_Supplement/N3.002.full所以Neurology2018 4月10;90 AB -目的:检查性能的全外显子组测序在先天性感觉和自主神经病变患者进行常规基因检测与负面的结果。背景:先天性受损感觉疼痛和温度与自主神经功能障碍患者的特点家族性神经异常(IKPBAP创始者突变引起的),先天性对疼痛的不敏感和无汗症(NTRK1基因的突变引起的),和其他遗传感官和自主神经病变(HSAN)。然而,这些突变被发现在许多患者出现先天性感官和自主赤字。设计/方法:我们招收11受损或缺失患者感觉疼痛和温度感觉发生在出生之前没有确认从HSAN基因分子诊断面板。我们进行详细的表型评估包括演讲、自主测试和全面的神经和眼科检查。结果:确定了基因变异10的11例(91%)。我们发现神经生长因子变异纯合子(n = 2、兄弟姐妹),SMPDL3A (n = 2、兄弟姐妹),LIFR (n = 2、兄弟姐妹),和TECPR2 (n = 1)从来没有发现在控制人口,并预测可能致病。我们还发现SCN10A杂合变异体(n = 1), SCN9A (n = 1)预测可能致病。一个病人有一个纯合子变体SCN11A不确定的致病性。基因检测是不确定只有一个病人。 Autonomic deficits included anhidrosis (SCN9A, NGF), hypohidrosis (TECPR2), hyperhidrosis (SCN11A, SCN10A, TECPR2, LIFR), alacrima/hypolacrima (SMPDL3A, TECPR2, LIFR), neurogenic dysphagia (TECPR2, SMPDL3A, SCN11A), gastroesophageal reflux (SCN11A), vomiting episodes (LIFR), central sleep apnea (TECPR2), and episodes of hypertension, tachycardia, hyperhidrosis and hypernatremia (LIFR).Conclusions: Whole exome sequencing can improve molecular diagnosis of congenital sensory and autonomic neuropathies and expand its genetic landscape. Further validation of some identified variants are required to confirm its definite pathogenicity.Study Supported by: National Institutes of Health (U54 NS065736) and Dysautonomia Foundation, Inc.Disclosure: Dr. Palma has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Palma has received personal compensation in an editorial capacity for Clinical Autonomic Research. Dr. Gao has nothing to disclose. Dr. Slaugenhaupt has nothing to disclose. Dr. Norcliffe-Kaufmann has nothing to disclose. Dr. Kaufmann has received personal compensation in an editorial capacity for Lundbeck Inc.

map