E1672 Sheynin et al. normal histamine flare response, sweated normally and had normal intelligence. Nerve conduction studies performed in 2 of the patients revealed normal motor conduction with borderline reduction in the medial plantar sensory action potential (SAP). Their corneal responses were reduced. The patients presented the clinical picture of CIP and had no features of other hereditary sensory neuropathies. Specifically, the phenotype differed from patients with Congenital Insensitivity to Pain with Anhydrosis (CIPA; MIM# 256800) in that all had normal cognitive development, lack of unexplained bouts of fever in infancy and early childhood, normal lacrimal product and sweat, and normal sympathetic skin responses. The study was approved by the Soroka Helsinki committee. See Supp. Methods for more information. Figure 1. Novel mutations identified in SCN9A. (a) Pedigree and haplotype around the SCN9A gene of the Israeli Bedouin family with the Nav1.7-R896Q mutation; (b) Pedigree for British singleton carrying the two mutations Nav1.7-ΔR1370-L1374 and Nav1.7- I1493SfsX8; (c) Schematic representation of the Nav1.7 sodium channel and locations of the identified mutations. The plasma membrane is shown in grey; transmembrane segments are labelled 1-6; the extracellular linkers between transmembrane segments 5 and 6 form the channel pore. Note that the Nav1.7-R896Q and Nav1.7-ΔR1370-L1374 mutations both map to similar regions of the channel in domain (D) 2 and 3 respectively. British patient The first child of healthy, non-consanguineous parents was referred aged one year for investigation for insensitivity to pain. The only complication of pregnancy or delivery was maternal fever 5 days prior to delivery that was treated with antibiotics. Birth weight was 4.2 kg and there were no obstetric or neonatal problems. First concerns were raised at age 6 months when she would bite her fingers during teething, showing no distress with the consequent injury. She had failed to show any discomfort with earlier childhood vaccinations. Subsequent injuries, including abrasion of her feet when learning to walk with a push-along walker and ulceration of her tongue following biting, similarly resulted in no distress. Aged 4 years she sustained a fracture to a right