1/32. A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.A nerve growth factor receptor encoded by the TRKA gene plays an important part in the formation of autonomic neurons and small sensory neurons in dorsal root ganglia and in signal transduction through its intracytoplasmic tyrosine kinase domain. Recently, three mutations in the tyrosine kinase domain of TRKA have been reported in patients with congenital insensitivity to pain with anhidrosis, which is an autosomal recessive disorder characterized by recurrent fever due to absence of sweating, no reaction to noxious stimuli, self-mutilating behavior, and mental retardation. We examined the TRKA gene in five generations of a large Japanese family with many consanguineous marriages who live in a small remote island of the southern part of japan. We found a novel point mutation at nucleotide 1825 (A-->G transition) resulting in Met-581-Val in the tyrosine kinase domain. Two of the three affected patients were homozygous for this mutation; however, the third affected patient was heterozygous. Further analysis revealed that the third patient was a compound heterozygote with the Met-581-Val mutation in one allele and with a single base C deletion mutation at nucleotide 1726 in exon 14 in the other allele, resulting in a frameshift and premature termination codon.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
2/32. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of unexplained fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. Human TRKA encodes a high-affinity tyrosine kinase receptor for nerve growth factor (NGF), a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. We have recently demonstrated that TRKA is responsible for CIPA by identifying three mutations in a region encoding the intracellular tyrosine kinase domain of TRKA in one Ecuadorian and three Japanese families. We have developed a comprehensive strategy to screen for TRKA mutations, on the basis of the gene's structure and organization. Here we report 11 novel mutations, in seven affected families. These are six missense mutations, two frameshift mutations, one nonsense mutation, and two splice-site mutations. Mendelian inheritance of the mutations is confirmed in six families for which parent samples are available. Two mutations are linked, on the same chromosome, to Arg85Ser and to His598Tyr;Gly607Val, hence, they probably represent double and triple mutations. The mutations are distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain. These data suggest that TRKA defects cause CIPA in various ethnic groups.- - - - - - - - - - ranking = 5keywords = nerve (Clic here for more details about this article) |
3/32. Congenital insensitivity to pain with anhidrosis: a case report.Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare genetic disorder of the peripheral nervous system characterized by recurrent episodes of unexplained fever, generalized anhidrosis, insensitivity to pain and temperature, and accompanied by self-mutilating behavior and mental retardation. We report on a 16 month-old boy with CIPA who exhibited these characteristic clinical features. A sural nerve biopsy revealed markedly reduced numbers of unmyelinated and small myelinated fibers, consistent with the characteristic features of CIPA.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
4/32. Multisystem involvement in congenital insensitivity to pain with anhidrosis (CIPA), a nerve growth factor receptor(Trk A)-related disorder.Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive disorder, is characterized by insensitivity to pain, self-mutilating behaviour, anhidrosis and recurrent hyperpyrexia. It is a hereditary sensory and autonomic neuropathy, also classified as HSAN, due to a defect of the receptor for nerve growth factor. CIPA is the first human genetic disorder caused by a defect in the neurotrophin signal transduction system. This is the first clinical report of CIPA patients characterized on molecular grounds. The clinical phenotypes of our patients show that CIPA is characterized by a multisystem involvement besides the nervous system, including bone fracture with slow healing, immunologic abnormalities, such as low response to specific stimuli, chronic inflammatory state ending in systemic amyloidosis. The molecular characterization allows a better understanding of most of the clinical features.- - - - - - - - - - ranking = 5keywords = nerve (Clic here for more details about this article) |
5/32. Congenital insensitivity to pain with anhidrosis. Report of a case and review of the literature.In a previous paper published in this journal, we reported two cases of "Congenital Sensory Neuropathy with Anhidrosis" with reference to the orthopedic complications (Theodorou et al., 1985). We now present a new typical case, under the currently used term: "Congenital Insensitivity to Pain with Anhidrosis" (CIPA) and a brief review of the literature on the incidence, etiology and problems arising in various systems. CIPA is an autosomal recessive form of sensory neuropathy manifesting with typical clinical features. Universal insensitivity to pain, anhidrosis or hypohidrosis, bouts of hyperpyrexia from very young age, self inflicted injuries, defective or absent lacrimation and mental retardation are specific diagnostic findings. Orthopedic, maxillofacial, dermatological and ophthalmologic complications are common. counseling of the family and school personnel for the prevention of injuries is necessary. early diagnosis is very important for the prevention and treatment of various complications. The etiology and pathogenesis of the condition is still unclear. The recent detection of a new gene, which encodes a receptor tyrosine kinase for nerve growth factor and lately of a specific point mutation associated with the gene inactivation11, may open new ways for the study and management of this disabling condition.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
6/32. Congenital insensitivity to pain with anhydrosis. Report of two unrelated cases.Two unrelated female cases of congenital insensitivity to pain with anhydrosis are presented. The first case was born from consanguineous parents. In both cases, onset of manifestation was observed in infancy with automutilation and recurrent fever. Both were mentally retarded. They underwent a peripheral nerve biopsy respectively at 3 and 33 years. A dramatic loss of unmyelinated fibers was observed in both cases. Myelinated fibers were also moderately reduced in number, especially those of smallest diameter; this loss was more marked in the second patient who was adult when the peripheral nerve was studied. Clusters of regenerating myelinated fibers were seen in both cases. Such histological observations might suggest a slowly progressive disorder. The cases are discussed together with previous reports dealing with congenital insensitivity to pain.- - - - - - - - - - ranking = 2keywords = nerve (Clic here for more details about this article) |
7/32. Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis.uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.- - - - - - - - - - ranking = 5keywords = nerve (Clic here for more details about this article) |
8/32. Raeder's syndrome.Raeder's paratrigeminal syndrome is a disorder manifested by unilateral ptosis, miosis, intact facial sweating, and severe pain in the distribution of the ophthalmic division of the fifth nerve. It is a clinical pattern where, usually, a middle-aged male gets a severe throbbing supraorbital headache accompanied by ptosis and miosis. The headache is intermittently present for several weeks or months. Facial sweating may or may not be affected. This report describes a female with Raeder's syndrome who had unilateral facial anhibrosis.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
9/32. The circadian rhythm of body core temperature (CRT) is normal in patient with congenital generalized anhidrosis.The temperature of the human body is not constant during the day, and is related to a double modulation of both homeostatic and circadian processes. The circadian rhythm of body core temperature (CRT) is known to depend on the central mechanism involved in thermoregulatory variations. The role of sweating in the nocturnal fall of body core temperature (BcT) is not clear. We evaluated the CRT in a 45-year-old female with a lack of sweating since birth because of congenital generalized anhidrosis. She referred episodes of heat intolerance when ambient temperature was around 35 degrees C. skin biopsies of both forearms and left axilla revealed atrophy and morphologic changes of eccrine glands. Neurological examination, nerve conduction studies, sympathetic skin response and cardiovascular reflex tests were normal. The study of CRT was performed by monitoring rectal temperature continuously in controlled conditions (ambient temperature 24 /- 1 degrees C and humidity 40-50% in a light-dark schedule). The rhythmometric analysis showed normal 24-hour fluctuations. This case represents an "experiment of nature"demonstrating that the physiological nocturnal fall of BcT is independent of sweating.- - - - - - - - - - ranking = 1keywords = nerve (Clic here for more details about this article) |
10/32. Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and histologic study.OBJECTIVE: To define the involvement of peripheral nerve fibers in Ross syndrome. methods: Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, h-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome. RESULTS: Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; h-reflex was absent at rest in all patients. hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients. CONCLUSIONS: Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers.- - - - - - - - - - ranking = 6keywords = nerve (Clic here for more details about this article) |
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