1/13. 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 = sweat (Clic here for more details about this article) |
2/13. 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 = 1keywords = sweat (Clic here for more details about this article) |
3/13. Congenital sensory neuropathy with anhidrosis (hereditary sensory neuropathy type IV).Hereditary sensory neuropathies comprise a group of rare childhood diseases which are classified into four types. We present a Greek boy 11 years old with hereditary sensory neuropathy type IV (congenital sensory neuropathy with anhidrosis) whom we have followed up and studied during the last seven years. Our patient presented for the first time with recurrent hyperthermic episodes without sweating, and lack of pain sensation from the first months of life. Insensitivity to pain and thermal stimuli had resulted in burns on the extremities and self-mutilation of the tongue, lips and fingertips. When he was five and seven years old respectively he had two painless fractures of the ankles which led to insoluble orthopedic problems. He also suffered from mental retardation, which was obvious from his first years of life. Sweat gland investigations showed significant hypohidrosis or anhidrosis although the sweat glands were normal microscopically. Hereditary sensory neuropathy type IV, although rare, is important for dermatologists because it must be differentiated from other anhidrotic syndromes, and in view of the poor prognosis of the condition.- - - - - - - - - - ranking = 8.1618118021195keywords = sweat gland, sweat, gland (Clic here for more details about this article) |
4/13. An infant with primary tooth loss and palmar hyperkeratosis: a novel mutation in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis.patients with congenital insensitivity to pain and anhidrosis (CIPA), caused by mutations in the NTRK1 gene, can be difficult to diagnose because of their variable presentation, the lack of simple diagnostic tests, and the paucity of cases reported in north america. We describe a 1-year-old infant who had tooth loss and palmar hyperkeratosis as the primary manifestations of CIPA. He was initially evaluated by a pediatric dentist and epidermal dysplasia syndromes were considered, but insensitivity to pain was suspected after a skeletal survey revealed an unrecognized skull fracture. Nerve conduction studies were normal, as was his response to subdermal histamine injection. sequence analysis of his NTRK1 gene revealed 2 mutations: 1 mutation is novel, while the other has been described previously in a patient of northern European descent. An antibody directed against NTRK1 revealed persistent expression in keratinocytes, consistent with the mutations in this patient. skin biopsy specimens revealed a lack of epidermal and sweat gland innervation. immunohistochemistry of skin biopsy specimens, together with routine nerve conduction studies, can provide quick and reliable confirmation if CIPA is clinically suspected.- - - - - - - - - - ranking = 7.1561059010597keywords = sweat gland, sweat, gland (Clic here for more details about this article) |
5/13. Two brothers with a variant of hereditary sensory neuropathy.We report two brothers with the clinical symptoms and neuropathological findings of hereditary sensory and autonomic neuropathy (HSAN) type IV but with normal sweating function and absence of recurrent fever. We propose that our patients may have a lower degree of expression of the genetic defect underlying HSAN type IV or that they represent a separate genetic entity.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
6/13. Congenital insensitivity to pain with anhidrosis: morphological and morphometrical studies on the skin and peripheral nerves.A rare case of congenital insensitivity to pain with anhidrosis is presented. The male patient, who expired at 17 years of age, was noted insensitive to pain and bouts of unexplained fever at birth. He frequently fractured the hands and feet with secondary osteomyelitis. He did not sweat even in warm season. The intradermal nerve fibres and sweat glands were normal in distribution. The peripheral nerve seemed to be almost normal with light microscopy but the electron microscopical study revealed extreme paucity of unmyelinated fibers and a reduction of myelinated fibres, especially of small caliber. Abundant collagen fibrils comprised the endoneurium. There were no regenerative and/or degenerative changes of axons and myelin sheaths. The pathology of the peripheral nerve was considered to be congenital. Our case might belong to a category of congenital sensory neuropathy with anhidrosis (Pinsky and Di George 1966), congenital insensitivity to pain with anhidrosis (Gillespie and Perucca 1960) or hereditary sensory neuropathy type IV (Dyck and Ohta 1975, Goebel et al 1980).- - - - - - - - - - ranking = 8.1561059010597keywords = sweat gland, sweat, gland (Clic here for more details about this article) |
7/13. Congenital insensitivity to pain with anyhydrosis: morphological studies of skin and peripheral nerves.Two male siblings born to consanguineous parents, with the diagnosis of congenital insensitivity to pain with anhydrosis are evaluated. The patients presented with unexplained bouts of fever, self-mutilation, repeated trauma and inability to sweat. physical examination revealed both siblings to be insensitive to pain and temperature. The electron microscopic study of the skin was unremarkable whereas sural nerve biopsies yielded an essential lack of unmyelinated fibers.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
8/13. Congenital insensitivity to pain with anhidrosis: case report.Congenital insensitivity to pain with anhidrosis is a rare disorder. A case of a male patient presenting with loss of pain and temperature sensation, lack of sweat, and mild mental retardation is described. Differential diagnosis with similar pathological conditions is presented. Although 15 similar cases have been reported in the medical literature, this is the first case in which the dental characteristics are described in detail and the dental treatment of patients is discussed.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
9/13. Congenital sensory neuropathy with anhydrosis-a case report and investigation of autonomic nervous system abnormalities.A review of the clinical profile of congenital sensory neuropathy with anhydrosis is presented. It is stressed that major diagnostic criteria of this recessively inherited condition should be limited to insensitivity to pain with normal tactile perception, anhydrosis, recurrent unexplained fever, self-mutilation, mental retardation, hypotonia, histologically normal sweat glands and variable autonomic abnormality. A case conforming to this description is reported and compared with 13 published cases. Special investigations of the autonomic nervous system through measurement of urinary catecholamine metabolites and psychophysiologic variables were conducted on this patient. Based on the analysis of 5 X 24-hour urine, values of metabolites of dopamine and epinephrine were normal. Metabolites of norepinephrine, such as 3-methoxy-4-hydroxy phenylglycol and normetanephrine, however, were significantly low when compared with those of four controls, suggesting decreased peripheral and central norepinephrine activity. Polygraph recording and evaluation of some orienting response components revealed no obvious signs of autonomic perturbation and, specifically, no phasic electrodermal activity. These two findings (biochemical and electrodermal) strongly suggest an autonomic imbalance, specifically component, both central and peripheral. It is suggested that autonomic disorder is an integral part of the syndrome and may be demonstrated by special investigations.- - - - - - - - - - ranking = 7.1561059010597keywords = sweat gland, sweat, gland (Clic here for more details about this article) |
10/13. Eccrine sweat glands are not innervated in hereditary sensory neuropathy type IV. An electron-microscopic study.The ultrastructural study of a skin biopsy in a patient afflicted with hereditary sensory neuropathy type IV (congenital insensitivity to pain with anhidrosis) did not reveal any unmyelinated axons or axonal terminals around eccrine sweat glands but only processes, partially covered by a basement membrane and therefore resembling Schwann cell processes. The absence of such unmyelinated axons in close proximity to eccrine sweat glands where they normally occur appears to be the morphological equivalent to the anhidrosis and also corresponds to the deficiency of unmyelinated axons in the sural nerve of the same patient, as previously reported.- - - - - - - - - - ranking = 42.936635406358keywords = sweat gland, sweat, gland (Clic here for more details about this article) |
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