Drenth Joost P H, te Morsche Rene H M, Guillet Gerard, Taieb Alain, Kirby R Lee, Jansen Jan B M J
Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
J Invest Dermatol. 2005 Jun;124(6):1333-8. doi: 10.1111/j.0022-202X.2005.23737.x.
Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm and painful hands, and/or feet. We previously localized the gene for primary erythermalgia to a 7.94 cM region on chromosome 2q. Recently, Yang et al identified two missense mutations of the sodium channel alpha subunit SCN9A in patients with erythermalgia. The presence of voltage-gated sodium channels in sensory neurons is thought to play a crucial role in several chronic painful neuropathies. We examined four different families and two sporadic cases and detected missense sequence variants in SCN9A to be present in primary erythermalgia patients. A total of five of six mutations were located in highly conserved regions. One family with autosomal dominantly inherited erythermalgia was double heterozygous for two separate SCN9A mutations. These data establish primary erythermalgia as a neuropathic disorder and offers hope for treatment of this incapacitating painful disorder.
原发性红斑性肢痛症是一种罕见的疾病，其特征为双手和/或双脚反复出现发红、发热和疼痛发作。我们之前将原发性红斑性肢痛症的基因定位到2号染色体q臂上一个7.94厘摩的区域。最近，Yang等人在红斑性肢痛症患者中鉴定出钠通道α亚基SCN9A的两个错义突变。感觉神经元中电压门控钠通道的存在被认为在几种慢性疼痛性神经病变中起关键作用。我们检查了四个不同的家族和两个散发病例，发现在原发性红斑性肢痛症患者中存在SCN9A的错义序列变异。六个突变中有五个位于高度保守区域。一个常染色体显性遗传红斑性肢痛症家族对两个不同的SCN9A突变呈双杂合状态。这些数据确定原发性红斑性肢痛症为一种神经病变，并为治疗这种使人丧失能力的疼痛性疾病带来了希望。
