RESUMO
Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease characterized by diffuse hyperkeratosis of the epidermis of the palm and sole with an erythematous margin. The Keratin 9 (KRT9) and Keratin 1 genes are responsible for EPPK. Several previous studies have focused on the genetic basis of EPPK; however, genetic anticipation has not yet been reported. We described a four-generation family with EPPK and identified a p.R163W mutation of KRT9. We observed a decrease in the age of onset in three consecutive generations in the family of the proband, indicating possible genetic anticipation in this familial EPPK. Further studies are needed to elucidate the mechanisms of anticipation in EPPK.
Assuntos
Antecipação Genética , Queratina-9/genética , Ceratodermia Palmar e Plantar Epidermolítica/genética , Mutação , Idade de Início , Substituição de Aminoácidos , Códon , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Ceratodermia Palmar e Plantar Epidermolítica/diagnóstico , Masculino , Linhagem , FenótipoRESUMO
Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Cardiopatias Congênitas/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Síndrome de Smith-Magenis/complicações , Síndrome de Smith-Magenis/genética , Criança , Pré-Escolar , China , Fácies , Feminino , Cardiopatias Congênitas/complicações , Humanos , Recém-Nascido , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the process of cell migration. Its expression has been considered as a bad prognostic indicator in stage I lung adenocarcinoma. However, the expression and clinical significance of myosin IIA in esophageal cancer has not been explored. In this study, we investigate the expression level of myosin IIA in 50 esophageal squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical staining and correlated its expression with clinicopathological features. Myosin IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30 adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin IIA expression level was significantly correlated with increasing metastatic lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further univariate analysis suggested that strong myosin IIA expression was associated with a significantly shorter overall survival (P = 0.021). In addition, MYH9 SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to study the role of myosin IIA in cell migration. SiRNA-mediated depletion of myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and attenuated cell migration ability (P = 0.000). In conclusion, these findings indicate that overexpression of myosin IIA may contribute to the progression and poor prognosis of esophageal squamous cancer, and this effect may be associated with increased cancer cell migration.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas Motores Moleculares/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina não Muscular Tipo IIA/metabolismo , Carcinoma de Células Escamosas/genética , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Junções Célula-Matriz/metabolismo , Neoplasias Esofágicas/genética , Humanos , Imuno-Histoquímica , Metástase Linfática , Proteínas Motores Moleculares/genética , Cadeias Pesadas de Miosina/genética , Miosina não Muscular Tipo IIA/genética , Miosina não Muscular Tipo IIA/fisiologia , Prognóstico , Interferência de RNA/fisiologia , RNA Interferente Pequeno , TransfecçãoRESUMO
Congenital heart defects (CHDs) occur in about 0.5-1% of all newborns and are the most common birth defects. Double outlet right ventricle (DORV) accounts for approximately 1-3% of all CHDs. Similar to Tetralogy of Fallot (TOF), DORV is a subtype of contruncal heart defects (CTDs) and is anatomically characterized by a malposition of the great arteries. We described a boy with chromosomal translocation: 46, XY t (8; 18) (q22; q21) that may disrupts the ZFPM2/FOG2 locus. The coding sequences of ZFPM2/FOG2 were determined in 38 patients with sporadic DORV, 95 patients with TOF, and 12 patients with transposition of the great arteries. Five DNA sequence variants affecting variably conserved residues of ZFPM2/FOG2 were identified in patients with TOF type or ventricular septal defect type of DORV. Three novel mutations (p.V339I, p.K737E, and p.A611T) were reported for the first time. The other two mutations (p.M703L and p.Q889E) were reported in patients with congenital diaphragmatic hernia but not in patients with CHD. Our finding suggests that variants of the ZFPM2/FOG2 gene might be a common cause of DORV.
Assuntos
Proteínas de Ligação a DNA/genética , Dupla Via de Saída do Ventrículo Direito/genética , Variação Genética , Fatores de Transcrição/genética , Adolescente , Sequência de Aminoácidos , Povo Asiático , Criança , Pré-Escolar , Cromossomos Humanos , Estudos de Coortes , Éxons , Feminino , Deleção de Genes , Frequência do Gene , Loci Gênicos , Hérnias Diafragmáticas Congênitas , Humanos , Cariotipagem/métodos , Masculino , Dados de Sequência Molecular , Mutação , Análise de Sequência de DNA , Tetralogia de Fallot/genéticaRESUMO
The regulation of vascular smooth muscle cells (VSMCs) function by taurine has been a subject of increasing interest and investigation, and taurine is taken up into cells through a specific transporter system, the taurine transporter (TAUT). In the present study, we examined the expression of TAUT in VSMCs and the kinetic parameters of the uptake process of TAUT in VSMCs. RT-PCR and western blot demonstrated that the mRNA and protein of TAUT was expressed in VSMCs in vitro. Immunohistochemistry using antibody for TAUT revealed the expression of this protein in rat thoracic aorta. The maximal [(3)H]taurine uptake rate in VSMCs was 37.75 +/- 3.13 pmol/min per mg of protein, with a K ( m ) value of 5.42 +/- 0.81 microM. Thus, VSMCs are able to express a functional taurine transporter. The regulation and detailed function of taurine and TAUT in VSMCs remain unclear, but our findings suggest a functional role for them in VSMCs metabolism.
