ABSTRACT
OBJECTIVE: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. SUBJECTS AND METHODS: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. RESULTS: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. CONCLUSION: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. Arq Bras Endocrinol Metab. 2012;56(9):646-52.
OBJETIVO: Investigar a presença de variantes nos genes TAC3 e TACR3, os quais codificam a NKB e seu receptor (NK3R), respectivamente, em uma coorte de pacientes com distúrbios puberais centrais idiopáticos. SUJEITOS E MÉTODOS: Duzentos e trinta e sete pacientes foram estudados: 114 com puberdade precoce central (PPC), 73 com hipogonadismo hipogonadotrófico isolado normósmico (HHI) e 50 com retardo constitucional do crescimento e desenvolvimento (RCCD). O grupo controle consistiu de 150 indivíduos brasileiros que apresentaram desenvolvimento puberal normal. O DNA genômico foi extraído de sangue periférico, e as regiões codificadoras dos genes TAC3 e TACR3 foram amplificadas e sequenciadas automaticamente. RESULTADOS: Uma variante (p.A63P) foi identificada na NKB, e quatro variantes, p.G18D, p.L58L (c.172C>T), p.W275X e p.A449S, foram identificadas no NK3R, as quais foram ausentes no grupo controle. A variante p.A63P foi identificada em uma menina com PPC, e a variante p.A449S, em uma menina com RCCD. As variantes previamente descritas, p.G18D, p.L58L e p.W275X, foram identificadas em três indivíduos com HHI normósmico do sexo masculino não relacionados. CONCLUSÃO: Variantes raras nos genes TAC3 e TACR3 foram identificadas em pacientes com distúrbios puberais centrais idiopáticos. Mutações de perda de função no gene TACR3 foram associadas com o fenótipo de HHI normósmico. Arq Bras Endocrinol Metab. 2012;56(9):646-52.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Growth Disorders/genetics , Hypogonadism/genetics , Neurokinin B/genetics , Puberty, Delayed/genetics , Puberty, Precocious/genetics , /genetics , Case-Control Studies , Cohort Studies , Polymorphism, Single Nucleotide/geneticsABSTRACT
Objective To examine the localization of neurokinin B receptor (NK3)\|like immunoreactivity (\|LI) in the central nervous system of the mouse. Methods An immunohistochemcial staining method was used. Results NK3 receptor\|LI was localized in somatic and dendritic profiles in the most parts and in neuropil in a few regions of the mouse central nervous system. A large number of neurons with NK3\|LI was seen in the anterior olfactory nuclei, accumbens nucleus, septal area, ventral pallidum, pallidum, caudate putamen, nucleus of the stria terminalis, anterior hypothalamic area, tuber cincreum area, lateral hypothalamic area, perifornical nucleus, supraoptic nucleus, arcuate nucleus, mammillar nuclei, substatia nigra, ventral tegmental area, retrorubral area, superior and inferior colliculus, periaqueductal gray, nucleus of the solitary tract, and superficial layers of the medullary and spinal dorsal horns. The superfical layers of the cerebral cortex, piriform cortex, dorsal hippocampus, amygdal complex, reticular formation of the brainstem contained some neurons with NK3 receptor\|LI. In the ventral hippocampus, median and intralaminar nuclei of the thalamus and interpeduncular nuclei, NKR\|LI was localized in neuropil. Conclusion\ Neurons with NK3 receptor\|LI were widely distributed in the central nervous system. It may be involved in many physiological functions in the central nervous system of the mouse.\;[