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1.
Sci Total Environ ; : 151261, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715222

RESUMO

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92-2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24-0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates. This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34267309

RESUMO

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear. OBJECTIVE: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children. METHODS: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture. RESULTS: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR)Q4 = 3.73, 95%CI [1.32, 11.04], ptrend = 0.003), dimethyl phosphate (DMP) (ORQ4 = 4.04, 95%CI [1.34, 12.94], ptrend = 0.014) and diethyl phosphate (ORQ4 = 2.61, 95%CI = [0.93, 7.66], ptrend = 0.030), and for the mixture of compounds (ORWQS = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%). CONCLUSIONS: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology.

4.
Sci Total Environ ; 773: 145604, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33592467

RESUMO

This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography-mass spectrometry (GC-MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 µg/g cre. vs. 18.41 µg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23-3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04-2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17-1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: -0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.


Assuntos
Arildialquilfosfatase , Transtorno do Deficit de Atenção com Hiperatividade , Arildialquilfosfatase/genética , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Criança , Cromatografia Líquida , Humanos , Organofosfatos/efeitos adversos , Estresse Oxidativo , Polimorfismo Genético , Espectrometria de Massas em Tandem
5.
Sci Total Environ ; 618: 635-644, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29055577

RESUMO

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQDEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (ß=-0.63 (-1.20 to -0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised.


Assuntos
Exposição Dietética , Dietilexilftalato/análise , Contaminação de Alimentos , Ácidos Ftálicos/urina , Adulto , Feminino , Humanos , Gravidez , Taiwan
6.
Pediatr Neonatol ; 59(4): 418-420, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29198617
7.
Sci Total Environ ; 607-608: 1126-1135, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28724251

RESUMO

Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03µg/g creatinine) (ß=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Exposição Materna/efeitos adversos , Organofosfatos/efeitos adversos , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Peso ao Nascer , Estatura , Estudos de Coortes , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Taiwan
8.
Int J Mol Med ; 39(5): 1195-1205, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28339008

RESUMO

Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with high-risk or recurrent MB respond poorly to current therapies, and have a higher related mortality. For this reason, potential molecules related to MB need be identified in order to develop targets for the development of novel therapeutics. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function 'vesicle' were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), was found to have significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells as shown by western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 altered the morphology and the chemotherapeutic effects of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. On the whole, our data indicate that the expression of SNAP25 is crucial for dendrite formation and is associated with the effects of targeted chemotherapy. The detection of SNAP25 expression in MB cells may thus be essential for the chemotherapeutic application of Ara-C.


Assuntos
Neoplasias Cerebelares/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Meduloblastoma/genética , Proteína 25 Associada a Sinaptossoma/genética , Transcriptoma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/metabolismo , Criança , Citarabina/farmacologia , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/metabolismo , Pessoa de Meia-Idade , Prognóstico , Proteínas SNARE , Proteína 25 Associada a Sinaptossoma/metabolismo , Análise Serial de Tecidos , Adulto Jovem
9.
Environ Res ; 149: 197-205, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27209343

RESUMO

On May 23, 2011, a major scandal involving the illegal use of phthalates as clouding agents in food products was reported. Specifically, di(2-ethylhexyl) phthalate (DEHP) was purposefully added to foods as a substitute emulsifier. The purpose of this study was to examine the effects of DEHP exposure on the growth characteristics of the child victims of this scandal. Eighty-eight victims, originating from northern, central, and southern Taiwan and ranging in age from 6.0 to 10.5 years, were invited to participate in this study during clinic visits. The participants underwent follow-up health examinations from August 2012 to February 2013. We collected information on each participant's history of exposure to tainted food products using a questionnaire, and we analyzed their urinary concentrations of DEHP metabolites using high-performance liquid chromatography/tandem mass spectrometry. These data were then used to estimate their daily DEHP intake (DIAll) during the scandal. We also measured physical development parameters (height, weight, and bone age) and hormone levels (thyroid, sex and growth hormones) to evaluate their overall growth characteristics. The average (SD) duration of DEHP intake from tainted nutrition supplements was 1.39 (1.01) years. The median DIAll values were 19.93 and 20.69µg/kg bw/day for boys and girls, respectively. Among the enrolled children, the DIAll values of 46.9% of boys and 51.3% of girls exceeded the reference dose (RfD) of 20µg/kg bw/day established by the US Environmental Protection Agency. Our results demonstrate that DIAll is negatively associated with the height percentile, weight percentile, bone age/chronological age, and insulin-like growth factor 1 (IGF-1) levels but not with IGF binding protein 3 (IGF-BP3) level, IGF-1/IGF-BP3, sex hormones, or thyroid hormone levels. The DEHP DIAll value exceeded the RfD at high rates among children of both genders. Our results suggest that high levels of DEHP exposure due to the consumption of tainted food products are negatively associated with body weight, height, bone age, and IGF-1 levels in children. The likelihood of delayed puberty among the affected children is therefore a reasonable concern, and further follow-up is required.


Assuntos
Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Dietilexilftalato/toxicidade , Exposição Ambiental , Poluentes Ambientais/toxicidade , Antropometria , Criança , Feminino , Contaminação de Alimentos , Humanos , Masculino , Taiwan
10.
Pediatr Neonatol ; 57(5): 431-435, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-24486081

RESUMO

Maple syrup urine disease (MSUD) is an autosomal recessive aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine). Accumulation of their corresponding keto-acids leads to encephalopathy if not treated in time. A newborn male patient was suspected to have MSUD after tandem mass study when he presented symptoms and signs suggestive neonatal sepsis, anemia, and diarrhea. Food restriction of BCAAs was started; however, acrodermatitis enteropathica-like skin eruptions occurred at age 2 months. The skin rashes resolved after adding BCAAs and adjusting the infant formula. At age 7 months, he suffered from recurrent skin lesions, zinc deficiency, osteoporosis, and kyphosis of the thoracic spine with acute angulation over the T11-T12 level associated with spinal compression and myelopathy. After supplementation of zinc products and pamidronate, skin lesions and osteopenia improved gradually. Direct sequencing of the DBT gene showed a compound heterozygous mutation [4.7 kb deletion and c.650-651insT (L217F or L217fsX223)]. It is unusual that neurodegeneration still developed in this patient despite diet restriction. Additionally, brain and spinal magnetic resonance imaging, bone mineral density study, and monitoring of zinc status are suggested in MSUD patients.


Assuntos
Doença da Urina de Xarope de Bordo/complicações , Doença da Urina de Xarope de Bordo/diagnóstico , Doenças da Medula Espinal/diagnóstico , Curvaturas da Coluna Vertebral/diagnóstico , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Doença da Urina de Xarope de Bordo/genética , Mutação , Doenças da Medula Espinal/complicações , Curvaturas da Coluna Vertebral/complicações
11.
Int J Hyg Environ Health ; 218(7): 603-15, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163779

RESUMO

BACKGROUND: Some phthalic acid esters (PAEs) and nonylphenol (NP) are endocrine-disrupting chemicals (EDCs) that are widely used in consumer products. Consequently, the general population is exposed simultaneously to both groups of chemicals. OBJECTIVE: To investigate the single- and co-exposure effects of PAEs (DMP, DEP, DnBP, DiBP, BBzP, and DEHP) and NP on obesity and pubertal maturity to compare the body sizes of general adolescents with the complainants of the phthalate-tainted foods scandal that occurred in Taiwan. METHODS: This study included 270 general adolescents aged 6.5-15.0 years and 38 complainants aged 6.5-8.5 years. Nine metabolites of the five PAEs and of NP were measured in urine. We used a questionnaire to evaluate pubertal maturity, measured anthropometric indices (APs) to assess body size, and collected urine samples to measure the two groups of chemicals. RESULTS: We found that urinary PAE metabolite concentrations (specifically, metabolites of DEP, DnBP, DiBP, and DEHP) were positively associated with the APs for abdominal obesity (including skinfold thickness, waist circumference, waist-to-height ratio, and waist-to-hip) and indicated a dose-response relationship. Mono-methyl phthalate (MMP) exposure was inversely associated with pubarche among boys. The daily intake of DEHP in general adolescents exceeded the reference doses (RfD-20 µg/kgbw/day) and tolerable daily intake (TDI-50 µg/kgbw/day) by 3.4% and 0.4%, respectively. No associations were observed between NP exposure or co-exposure and the APs or pubertal maturity. No significant differences were observed between general adolescents and the complainants with regard to weight, height, or BMI. CONCLUSIONS: The study suggests that PAE (specifically, DEP, DnBP, DiBP, and DEHP) exposure is associated with abdominal obesity in adolescents and that the APs for abdominal obesity are more sensitive than BMI for measuring obesity among adolescents. We suggest that the RfD and TDI for PAEs should be revised to provide sufficient protection.


Assuntos
Peso Corporal/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Obesidade Pediátrica/etiologia , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Puberdade/efeitos dos fármacos , Adolescente , Antropometria , Tamanho Corporal/efeitos dos fármacos , Criança , Dietilexilftalato/efeitos adversos , Dietilexilftalato/urina , Disruptores Endócrinos/urina , Exposição Ambiental/análise , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/urina , Feminino , Contaminação de Alimentos , Humanos , Masculino , Obesidade Abdominal/etiologia , Obesidade Abdominal/urina , Obesidade Pediátrica/urina , Fenóis/urina , Ácidos Ftálicos/urina , Valores de Referência , Caracteres Sexuais , Taiwan
13.
PLoS One ; 9(8): e104245, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25148048

RESUMO

BACKGROUND: Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. METHODS: A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. RESULTS: In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (ß = -0.23 mIU/ml, p<0.01). CONCLUSION: This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy.


Assuntos
Disruptores Endócrinos/efeitos adversos , Hormônios Esteroides Gonadais/sangue , Exposição Materna/efeitos adversos , Fenóis/efeitos adversos , Adulto , Estudos de Coortes , Disruptores Endócrinos/urina , Feminino , Humanos , Pessoa de Meia-Idade , Fenóis/urina , Gravidez , Fatores de Risco , Taiwan , Adulto Jovem
14.
J Biomed Sci ; 21: 76, 2014 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-25139335

RESUMO

BACKGROUND: The immune system of newborn is generally depressed by impaired production of Th1-cell associated cytokines, which results in increased susceptibility to intracellular pathogens and poor response to vaccinations. For avoiding abortion, the maternal and fetal immune systems tend to Th2-cell polarizing cytokines. Besides, IL-12p35 is a determining factor of the bioactivity of IL-12, which has an important role in the Th1 response. Recently methylated DNA is known to associate to inhibit transcription. Therefore, we explored the methylation status of CpG sites upstream of the coding sequence of the IL-12p35 gene to determine whether neonatal peripheral blood mononuclear cell (PBMC) synthesis lower level of IL-12 is related to methylated DNA. RESULTS: PBMCs from adults expressed higher levels of IL-12p40 (p = 0.303) and IL-12p70 (p = 0.045) and had a strong ability to produce IL-12p35 mRNA (p = 0.01). However, there was no difference in the methylation status of CpG sites in the promoter of IL-12p35 between adults and newborns. CONCLUSIONS: We found that PBMC synthesis of bioactive IL-12p70 was significantly impaired in the neonatal period, potentially though a reduction in IL-12p35 production. The reeducation in IL-12p35 production might not be due to methylation of the promoter gene. But, the impairment of IL-12p35 expression during the neonatal period might be caused by other epigenetic regulation occurs in the chromatin level.


Assuntos
Envelhecimento/imunologia , Ilhas de CpG/imunologia , Metilação de DNA/imunologia , Epigênese Genética/imunologia , Subunidade p35 da Interleucina-12/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Envelhecimento/genética , Cromatina/genética , Cromatina/imunologia , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Humanos , Recém-Nascido , Subunidade p35 da Interleucina-12/genética , Masculino , Células Th1/citologia , Células Th2/citologia
15.
Pediatr Neonatol ; 55(3): 213-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24268812

RESUMO

BACKGROUND: Maple syrup urine disease (MSUD) is a rare inborn error of metabolism caused by a deficiency of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Mutations in any one of the three different genes encoding for the BCKD components, namely, BCKDHA, BCKDHB, and DBT, may be responsible for this disease. In Taiwan, few MSUD cases were diagnosed clinically, and most of these patients are from Aboriginal tribes. MATERIALS AND METHODS: To identify and detect the carrier frequency of MSUD in Taiwanese Aboriginal tribes, we performed biochemical and molecular studies from peripheral blood in MSUD patients and dried blood on filter paper in the enrolled screened populations. RESULTS: Homozygous A208T and I281T of BCKDHA were found in two patients from Hans (non-Aboriginal Taiwanese), respectively; compound heterozygous mutations of the DBT gene [4.7 kb deletion/c.650-651insT (L217F or L217fsX223) and c.650-651insT/c.88-89delAT] were found in two patients from Amis, respectively, after direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism studies. There were no cases of deleted 4.7-kb heterozygote out of 302 normal people (Hans, n = 125; Atayal, n = 156; and Saisiyat, n = 21); by contrast, the DBT mutations c.650-651insT and deleted 4.7-kb heterozygote were noted in 2/121 and 1/121, respectively, from the general population of the Amis, a southeastern Taiwanese tribe. CONCLUSION: Although the Taiwanese Austronesian Aboriginal tribes are considered to share a common origin, different gene preferences of MSUD were noted. The novel DBT mutation c.650-651insT was more prevalent than the deleted 4.7-kb heterozygote in the Amis population. The reported 4.7-kb deletion indicating a possible founder mutation may be preserved in the southern and eastern, but not in northern Aboriginal tribes of Taiwan.


Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aciltransferases/genética , Doença da Urina de Xarope de Bordo/etnologia , Doença da Urina de Xarope de Bordo/genética , Mutação , Grupo com Ancestrais Oceânicos/etnologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/etnologia , Feminino , Efeito Fundador , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Taiwan/epidemiologia , Adulto Jovem
17.
Pediatr Neonatol ; 54(3): 198-201, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23597553

RESUMO

Restrictive dermopathy (RD) is a rare and lethal autosomal recessive syndrome characterized by very tight, thin, and easily eroded skin and contracture of joints. We present two siblings in a family. Case 1, a female neonate, showed mild characteristic presentations of RD and survived for 16 days, and Case 2, a male neonate, was stillborn with typical severe features of RD. His skin biopsy showed typical histological findings, and genetic study revealed a homozygous nonsense mutation on the exon 6 of zinc metalloproteinase STE24 (ZMPSTE24). The exact pathogenic mechanism of RD remains poorly understood. The most recent studies on mutations in lamin A and/or ZMPSTE24 have shed some light on the pathophysiology of RD and may help direct the development of future therapeutic approaches.


Assuntos
Contratura/genética , Anormalidades da Pele/genética , Feminino , Humanos , Recém-Nascido , Lamina Tipo A/genética , Masculino , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Mutação , Irmãos
18.
Am J Med Genet A ; 155A(7): 1511-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21671394

RESUMO

Kabuki syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki syndrome is caused by mutations in MLL2, a gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin states. Here, we report on the screening of 110 families with Kabuki syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki syndrome.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Doenças Hematológicas/genética , Mutação/genética , Proteínas de Neoplasias/genética , Doenças Vestibulares/genética , Anormalidades Múltiplas/diagnóstico , Alelos , Face/anormalidades , Ordem dos Genes , Testes Genéticos , Genótipo , Doenças Hematológicas/diagnóstico , Humanos , Fenótipo , Prognóstico , Doenças Vestibulares/diagnóstico
19.
Indian J Pediatr ; 78(7): 826-32, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21287369

RESUMO

OBJECTIVE: To report clinical experiences and cytogenetic findings of transient myeloproliferative disorder (TMD) in neonates with and without Down syndrome (DS). METHODS: GATA1 gene was screened in DNA samples from neonates presenting with TMD during their leukemic and remission status. RESULTS: Six neonates (2 phenotypically normal and 4 DS) born in the past 6 years had presented with TMD; all had trisomy 21 during leukemic status. Two DS infants died during early infancy, one of hepatic failure and one of cardiac complication. One non-DS infant evolved into myelodysplastic syndrome (MDS) and acute leukemia since 14 months old. Three other patients have not developed true leukemia after follow-up of 8, 9, and 70 months, respectively. The authors detected mutations within exon 2 of GATA1 gene in 3 DS and 2 non-DS infants. All these mutations disappeared after remission of TMD, but an identical mutation was detected in one non-DS patient when evolving into MDS. Trisomy 21 was confined to leukemic clone in non-DS patients. CONCLUSIONS: TMD should be considered in case of congenital leukemia with megakaryoblastic features and accompanied by trisomy 21 and GATA1 mutation. Both DS and non-DS patients will possibly develop true leukemia within few years.


Assuntos
Síndrome de Down/genética , Fator de Transcrição GATA1/genética , Transtornos Mieloproliferativos/genética , Síndrome de Down/complicações , Feminino , Humanos , Recém-Nascido , Leucemia Megacarioblástica Aguda/complicações , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/genética , Masculino , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/diagnóstico , Regressão Neoplásica Espontânea , Mutação Puntual , Reação em Cadeia da Polimerase , Estudos Prospectivos
20.
Chang Gung Med J ; 33(4): 436-42, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20804673

RESUMO

BACKGROUND: A majority of the children with Prader-Willi syndrome (PWS) have global developmental delay and mental delay. The aim of this study was to investigate the developmental profiles and mental assessments among preschool children with PWS. METHODS: Ten children with PWS between the ages of 15 months to 6 years, and 11 children with typical development were enrolled. Developmental profiles in terms of their developmental quotient (DQ) for the eight domains of the Chinese Children Developmental Inventory (CCDI) and mental assessments in terms of intelligence quotient (IQ) and developmental index (DI) were carried out for all children. RESULTS: The DQs of all eight domains, including gross motor, fine motor, expressive language, concept comprehension, situation comprehension, self help, personal- social and general development, in the PWS group were lower than the DQs of the children from the typical development group (p < 0.01). Children with PWS had better DQs in the fine motor domain than in the gross motor domain and in the receptive language domain than in the expressive language domain. Furthermore, their verbal IQ were better than their performance IQ and their mental DI was better than their psychomotor DI. CONCLUSIONS: These findings suggest that the children with PWS show an uneven global developmental delay together with an uneven mental delay. The results of this study should allow clinicians to better understand the developmental functioning of children with PWS and this will help with the planning of treatment strategies.


Assuntos
Desenvolvimento Infantil , Síndrome de Prader-Willi/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inteligência , Masculino , Destreza Motora
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