RESUMO
Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities. The prevalence ranges from 1:100,000 to as high as 1:10,000. Most cases (50-60%) were carried mutation in NIPBL gene. To our knowledge this is the first CdLs Indonesian case that reported with molecular analysis study. We present an 11 months old female Indonesian patient with classic CdLs with congenital hypothyroid. Genetics studies were performed in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Thyroid studies (T3, T4, TSH and thyroid scan) were performed. Low level of T3 and T4, and high level of TSH were observed. Thyroid agenesis was found in thyroid scan examination. We detected thyroid agenesis which has been never reported in CdLs patients. We could not find any mutation in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Further genetics examinations were necessary whether there is mutation in other locus.
Assuntos
Hipotireoidismo Congênito/diagnóstico , Síndrome de Cornélia de Lange/diagnóstico , Disgenesia da Tireoide/diagnóstico , Proteínas de Ciclo Celular , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/patologia , Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/patologia , Feminino , Expressão Gênica , Humanos , Indonésia , Lactente , Proteínas/genética , Proteínas/metabolismo , Disgenesia da Tireoide/genética , Disgenesia da Tireoide/patologia , Tireotropina/genética , Tireotropina/metabolismo , Tiroxina/deficiência , Tiroxina/genética , Tri-Iodotironina/deficiência , Tri-Iodotironina/genética , Regulação para CimaRESUMO
Non-syndromic cleft palate only (NS CPO) is one of the most common congenital malformations that affect between 1 in 1000 - 2500 live births worldwide. The etiopathogenesis of clefts including NS CPO has been widely studied but is still poorly understood. NS CPO is considered to be a genetically complex, multifactorial disease. Based on several studies, mutations of TGFß3 gene emerged as the strong candidate gene associated with NS CPO. The purpose of this study was to analyze the relationship between the TGFß3 / SfaN1 gene variant and the risk of NS CPO in Indonesian patients. This study was case control design using samples from 31 NS CPO subjects and 35 control subjects. DNA was extracted from venous blood and the segment of TGFß3 gene/ SfaN1 were amplified by using polymerase chain reaction (PCR) technique, then digestion products by SfaN1 restriction enzyme which can detect locus of gene variant / polymorphism from restriction fragment length polymorphisms (RFLP) method were evaluated. The results indicated that the gene variant as substitution of base G into A was identified in TGFß3 gene and the frequency of heterozygous mutant GA genotype was 63,6% in NS CPO subjects and 36,4% in control subjects. The frequency of heterozygous mutant GA genotype was associated with increased risk of NS CPO (odds ratio (OR) = 2,260, 95% CI = 0,592 - 8,625). In conclusion, TGFß3 gene / SfaN1 polymorphism can be considered as the risk factor associated with NS CPO in Indonesian patients.
Assuntos
Fissura Palatina/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta3/genética , Alelos , Sequência de Bases , Sítios de Ligação/genética , Fissura Palatina/patologia , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Frequência do Gene , Genótipo , Humanos , Indonésia , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Fator de Crescimento Transformador beta3/metabolismoRESUMO
Increased telomerase activity is proposed to be related with the proliferation of some gastrointestinal cancers, including colorectal adenocarcinoma. To date, little is known about the activity of telomerase in different clinical stagings of colorectal adenocarcinoma, which may reflect its association with the progression of colorectal adenocarcinoma. We will examine the activity of telomerase enzyme in different clinical stagings of colorectal adenocarcinoma to know whether it has diagnostic and prognostic value as a tumor marker in the management of colorectal adenocarcinoma. The telomerase activities of primary tumor and normal adjacent mucosa in 17 cases with different clinical stagings of colorectal adenocarcinoma were measured by TRAP assay during the period of 28 September 1998 to 28 February 1999. The activities of the enzyme were measured both qualitatively and quantitatively, and the diagnostic value was assessed by diagnostic test using 2 x 2 table contingency. The association between telomerase activities and other related factors were assessed by multivariate analysis. Increased telomerase activities were found in 82.4% (14/17) of colorectal adenocarcinoma, but in only 23.5% (4/17) of normal adjacent mucosa, which was significantly higher (p = 0.008) compared to that of normal mucosa. The mean values of telomerase activity between different clinical stagings were 0, 0.661, and 1.449 units/410 (g protein for Dukes' stage B, C, and D, respectively, which gave p value of 0.025 with ANOVA. Using a cut off level of 0.2-units/410 (g protein for positive activity, we revealed that the accuracy, sensitivity, and specificity were 77.77%, 82.35%, and 76.47%, respectively. There was no association found between the histopathologic grading of the tumor and telomerase activity. Increased telomerase activity was found in colorectal adenocarcinoma compared to the adjacent normal mucosa. Telomerase activity correlates well with the progression of colorectal adenocarcinoma. Therefore, telomerase enzyme may have a potential diagnostic and prognostic values in the management of colorectal adenocarcinoma.
