To analyze the clinical manifestations and gene mutations in children with congenital insensitivity to pain with anhidrosis (CIPA), and review related literature. An infant diagnosed with congenital insensitivity to pain with anhidrosis was reported. The main clinical manifestations of the infant were painless, no sweat, and repeated fever. Peripheral blood of the infant and his parents was collected, and candidate variants were confirmed by Sanger sequencing. The results of molecular genetic analysis showed that there were compound heterozygous mutations (c.36G>A, c.851-33T>A) of neurotrophic tyrosine kinase receptor type 1 (NTRK1) in the infant. c.36G>A and c.851-33T>A were inherited from his father and mother, respectively. c.851-33T>A is a previously reported mutation, c.36G>A is an unreported mutation, which can lead to the tryptophan changing into a stop codon. According to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines, the mutation is interpreted as pathogenic, and the biological hazard is potentially harmful. Congenital insensitivity to pain with anhidrosis is a rare inherited disorder. Genetic molecular genetic analysis is helpful to diagnose and discover new gene mutations.
Channelopathies ; Humans ; Infant ; Mutation ; Pain Insensitivity, Congenital ; Receptor, trkA

Female ; Humans ; Infant ; Mutation ; Pain Insensitivity, Congenital ; complications ; genetics ; pathology ; Receptor, trkA ; genetics

Humans ; Receptor, trkA/genetics* ; Neoplasms/genetics* ; Biomarkers, Tumor ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics*

Humans ; Nerve Growth Factor ; physiology ; Pain ; physiopathology ; Pulpitis ; physiopathology ; Receptor, Nerve Growth Factor ; physiology ; Receptor, trkA ; physiology

TrkA is essential components of the high-affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF. Here we report on the expression of trkA in the cerebral cortex and diencephalon of mongolian gerbils during postnatal development. The expression of trkA was identified by immunohistochemical method. In parietal cortex and piriform cortex, higher levels of trkA-IR (immunoreactivity) were detected at 3 days postnatal (P3) and at P9. Although trkA was not expressed till P3 in the parietal cortex, it was detectable at birth in the piriform cortex. Several regions, such as Layers I, IV & VI, did not show much expression. Layer I showed especially weak labeling. In the hippocampus, thalamus, and hypothalamus, higher levels of trkA-IR were detected at P6 and P12 than earlier days. But trkA was not expressed at birth in the hippocampus, at P3 in the reticular thalamic nucleus (Rt), or neonatally in the dorsomedial hypothalamic nucleus (DM). This data shows that expression of trkA is developmentally regulated and suggests that high affinity neurotrophin-receptors mediate a transient response to neurotrophines in the cerebral cortex and diencephalon during mongolian gerbil brain ontogeny.
Animals ; Animals, Newborn ; Cerebral Cortex/*metabolism ; Diencephalon/*metabolism ; Gerbillinae/*metabolism ; Immunohistochemistry/veterinary ; Nerve Growth Factor/metabolism ; Receptor, trkA/*metabolism

OBJECTIVETo screen for mutations of NTRK1 gene in a Chinese family affected with congenital insensitivity to pain with anhidrosis (CIPA).

METHODSGenomic DNA was extracted from the proband and her family members. All of the 17 exons and intron-exon boundaries of the NTRK1 gene were analyzed by direct Sanger sequencing. For the deletional mutation, the PCR products were subjected to T-A cloning and sequencing to verify the mutation.

RESULTSNTRK1 gene analysis revealed that proband has carried a c.1786C>T (p.Arg596*) nonsense mutation inherited from her mother and a novel deletional mutation c.1928-2028+23del from her father. Her elder brother only carried the deletional mutation.

CONCLUSIONThe diagnosis of CIPA relied on typical clinical symptoms of no pain, anhidrosis and intellectual disability and detection of the biallelic NTRK1 mutations. The novel deletional mutation has enriched the spectrum of NTRK1 mutations.

Child, Preschool ; DNA Mutational Analysis ; Exons ; Female ; Hereditary Sensory and Autonomic Neuropathies ; diagnosis ; genetics ; Humans ; Mutation ; Receptor, trkA ; genetics

Humans ; Clinical Relevance ; Receptor, trkA/genetics* ; Neoplasms ; Digestive System Neoplasms/genetics* ; Oncogene Proteins, Fusion/genetics* ; Gene Fusion

OBJECTIVETo determine the effect of tyrosine kinase A (TrkA) and vascular endothelial growth factor receptor 2 (VEGFR2) in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC).

METHODSThe expression of TrkA and VEGFR2 were detected by immunohistochemical staining in 47 cases of SACC of salivary glands. Clinical data were reviewed by multivariate prognostic analysis.

RESULTSThe positive rate of TrkA and VEGFR2 in SACC was 87.23% (41/47) and 85.11% (40/47) respectively. Express of TrkA and VEGFR2 in perineural invasion and recurrence group were higher than non-perineural invasion and non-recurrence group. Significant difference was found in microvessel density (MVD) and VEGFR2 expression within different groups (P < 0.05). MVD in perineural invasion group (25.14 +/- 2.83) was significantly higher than that in none perineural invasion group (18.81 +/- 1.33) (P < 0.05). MVD in recurrence or metastasis group (26.58 +/- 2.38) was significantly higher than that (19.06 +/- 1.39) in none recurrence nor metastasis group (P < 0.05).

CONCLUSIONPositive correlation between expression of TrkA, VEGFR2 and nerve invasion and vessel metastasis of SACC indicate that TrkA and VEGFR2 play important roles in the invasion and metastasis of SACC. It is possible that TrkA and VEGFR2 could be an aid for evaluating the prognosis of SACC patients.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Humans ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Receptor, trkA ; metabolism ; Salivary Gland Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor Receptor-2

Tyrosine kinase A (TrkA)is an essential component of the high affinity nerve growth factor (NGF) receptor necessary to the mediate the biological effects of the neurotrophins, NGF. This study examined the distribution of TrkA-immunoreactivity (IR)cells in the postnatal rat cerebral cortex and the changes that occur in postnatal development as a result of the expression of this protein. TrkA-IR was detected at postnatal day (PD)3, PD6, PD9 and PD15. Base upon their somatodendritic morphology, the most commonly labeled cell type was the pyramidal neurons. At PD3 and PD6, layer I, II, III and V was immunopositive for TrkA, at PD9, not only at layer I, II, III, and V but also at layer VI. At PD15, the TrkA-positive cells were distributed in all layers. These TrkA-positive cells were not detected at PD0. In contrast, there was significant increase in the percentage of cells exhibiting TrkA-IR with development and the highest level was detected at PD15. These results suggest that the cerebral cortex expresses TrkA strongly during the postnatal period. Moreover, the postnatal development-related increase in the expression of TrkA-cells shows that NGF may have a trophic effect on these cerebral cortex neurons from the postnatal period.
Animals ; Animals, Newborn ; Cerebral Cortex/*growth&development/*metabolism ; Gene Expression Regulation, Developmental/*physiology ; Neurons/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA/*metabolism

OBJECTIVETo screen for mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1) gene in a Chinese family affected with congenital insensitivity to pain with anhidrosis (CIPA).

METHODSWith informed consent obtained, peripheral blood samples were obtained from the patient and his family members. Seventeen coding exons and intron-exon boundaries of the NTRK1 gene were amplified with PCR and analyzed by direct sequencing.

RESULTSA novel mutation c.2086_2087insC (p.Arg696 fsx) was identified in exon 16 of the NTRK1 gene in the proband. This insertion has caused open reading frame shifting and a premature termination has occurred just one codon downstream. Truncation of 72 amino acids at the C terminus has wiped out part of the tyrosine kinase domain (TKD) of the protein. Both of the proband's parents and two grandmothers have carried the c.2086_2087insC (p.Arg696 fsx) mutation. No mutation was found in the NTRK1 gene of other siblings.

CONCLUSIONMutation analysis of the NTRK1 gene has been carried out in a Chinese family affected with CIPA, and a novel NTRK1 gene mutation was identified.

Base Sequence ; Child, Preschool ; DNA Mutational Analysis ; Exons ; genetics ; Hereditary Sensory and Autonomic Neuropathies ; genetics ; Humans ; Male ; Mutation ; Polymerase Chain Reaction ; Receptor, trkA ; genetics