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1.
Arq Bras Cir Dig ; 32(3): e1448, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644668

RESUMO

INTRODUCTION: Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial. AIM: To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk. METHODS: The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR. RESULTS: A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall. CONCLUSIONS: The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.


Assuntos
Doença de Hirschsprung/genética , Polimorfismo Genético/genética , Predisposição Genética para Doença , Doença de Hirschsprung/etnologia , Humanos , Proteínas Proto-Oncogênicas c-ret/genética , Sensibilidade e Especificidade
2.
Am J Med Genet A ; 173(4): 1066-1070, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28328136

RESUMO

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.


Assuntos
Transtornos Testiculares 46, XX do Desenvolvimento Sexual , Cromossomos Humanos Par 22/química , Doenças Desmielinizantes/genética , Doença de Hirschsprung/genética , Falência Renal Crônica/genética , Doença de Pelizaeus-Merzbacher/genética , Síndrome de Waardenburg/genética , Afro-Americanos , Duplicação Cromossômica , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/etnologia , Doenças Desmielinizantes/patologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/etnologia , Doença de Hirschsprung/patologia , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etnologia , Falência Renal Crônica/patologia , Masculino , Doença de Pelizaeus-Merzbacher/diagnóstico , Doença de Pelizaeus-Merzbacher/etnologia , Doença de Pelizaeus-Merzbacher/patologia , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/diagnóstico , Síndrome de Waardenburg/etnologia , Síndrome de Waardenburg/patologia
3.
Int J Clin Exp Pathol ; 8(5): 5528-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26191260

RESUMO

BACKGROUND: Genetic mosaicism has been reported for both coding and non-coding sequences in the RET gene in Hirschsprung disease (HSCR) patients. This study aimed to investigate somatic mutation rate in Chinese population by comparing both homozygous genotype percentage and risk allele frequency of 3 RET single nucleotide polymorphisms (SNPs) among blood and colon samples. METHODS: DNA was extracted from 59 HSCR blood samples, 59 control blood samples and 76 fresh frozen colon tissue samples (grouped into ganglionic, transitional and aganglionic level). Genotype status of rs2435357 and rs2506030 was examined by competitive allele specific hydrolysis probes (Taqman) PCR technology, and rs2506004 was examined by Sanger sequencing. Homozygous genotype percentage and risk allele frequency were calculated for each type of sample and compared by chi-square test. P<0.05 was regarded as being statistically significant. RESULTS: Colon tissue DNA samples showed similar frequency of SNPs as that of the blood DNA samples in HSCR patients, both of which are significantly higher than the control blood group (rs2435357 TT genotype: 71.2%, 74.7% versus 22.0% in HSCR blood, HSCR colon and control blood DNA respectively, P=0.000; rs2506004 AA genotype: 72.4%, 83.1% versus 25.5%, P=0.000; rs2506030 GG genotype: 79.7%, 77.2% versus 54.2%, P=0.000 and 0.004). With respect to DNA extracted from ganglionic, transitional and aganglionic levels, no statistically significant difference was demonstrated in those 3 regions (rs2435357: P=0.897; rs2506004: P=0.740; rs2506030: P=0.901). CONCLUSION: Our data does not support the notion that high frequency of somatic changes as an underlying etiology of Chinese HSCR population.


Assuntos
Doença de Hirschsprung/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-ret/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/etnologia , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Mosaicismo , Razão de Chances , Fenótipo , Fatores de Risco
4.
Dig Dis Sci ; 60(5): 1232-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25424204

RESUMO

BACKGROUND: Previous studies suggested that cytochrome P450 participated in the tumor metastasis and migration. CYP2B6 also acts as an important enzyme which metabolize partially or primarily metabolism of drugs, environmental contaminants, and mutagens. The objective of this study was to investigate the influence of CYP2B6 polymorphism on susceptibility of Hirschsprung disease. METHODS: TaqMan assay was performed to determine the genotypes of CYP2B6 rs707265, rs1042389, rs2054675 in 262 cases and 290 control subjects. Logistic regression was used to assess the associations between these polymorphisms and HSCR. RESULTS: We observed a significant association of CYP2B6 rs707265 (G>A) polymorphism and HSCR susceptibility (p < 0.001). Besides, rs707265 A presented a significant risk of HSCR (p < 0.001). CONCLUSIONS: Our result suggested that CYP2B6 rs707265 modified the risk of HSCR.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Citocromo P-450 CYP2B6/genética , Doença de Hirschsprung/genética , Polimorfismo Genético , Estudos de Casos e Controles , China/epidemiologia , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Doença de Hirschsprung/enzimologia , Doença de Hirschsprung/etnologia , Humanos , Modelos Logísticos , Razão de Chances , Fenótipo , Fatores de Risco
5.
J Hum Genet ; 57(5): 286-93, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22377709

RESUMO

Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric nervous system known to be associated with the RET-protooncogene and other candidates. Recently, a genome-wide association study has added NRG1, a regulator of the development of the enteric ganglia precursors, as a new candidate gene. The aim of this study is to validate the association of the RET-protooncogene and the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide polymorphism (SNP) genotyping and PCR-restriction fragment length polymorphism for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene) and rs2439305 (NRG1) showed the strongest associations with the disease at P-values of 8.17E-09 (odds ratio (OR)=6.43, 95% confidence intervals (CI)=3.33-12.40) and 6.94E-03 (OR=3.28, 95% CI=1.28-8.38), respectively. The RET-protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG genotype) was strongly associated with an increased risk of HSCR with a P-value of 1.99E-04 (OR=20.34, 95% CI; 2.54-162.78) when compared with a single SNP of the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and NRG1 is involved in the risk of HSCR development in the Thai population. Moreover, the study also detected a combined effect of SNPs by SNP-SNP interaction, which may help in predicting HSCR risk.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Doença de Hirschsprung/genética , Neuregulina-1/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-ret/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Doença de Hirschsprung/etnologia , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Tailândia/etnologia , Adulto Jovem
6.
J Pediatr Surg ; 47(2): 299-302, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22325379

RESUMO

BACKGROUND: Clinical association between Hirschsprung disease (HD) and Down syndrome (DS) is well established. RET promoter and intron 1 variations have been shown to interfere with RET function, increasing the risk of HD pathogenesis. The intronic single-nucleotide polymorphism 2 (SNP2 [rs2435357]) has been associated with DS-associated HD (DS-HD). This study focuses on variations of specific RET intron, 1 SNPs (viz, SNP1 [rs2506004] and SNP2 [rs2435357]) in DS-HD. PATIENTS AND METHODS: DNA was extracted from paraffin-embedded tissue samples and whole blood in 14 patients with DS with histologically proven HD. Polymerase chain reaction products of RET intron 1 were screened for genetic variation and matched to DS and controls from the general population. RESULTS: Thirty-seven blood and/or tissue from 14 patients with DS-HD were investigated. RET intronic variations (SNP1 [rs2506004] or SNP2 [rs2435357]) were detected in all patients. SNP1 was detected in all patients, was heterozygous in 9, and homozygous in 5 samples (all aganglionic and 1 total colonic aganglionosis). SNP2 was absent in 6 patients, heterozygous in 6, and homozygous in 3. Three DS controls had a heterozygous SNP1. Homozygous intronic SNP RET variations were related to aganglionic tissue but not normally ganglionated or transitional zone from the same individual. CONCLUSIONS: Potential disease-related RET mutations were identified in the intron region in 80% of patients with DS-HD investigated, suggesting a causal relationship. The presence of a homozygous form in the aganglionic tissue probably represents a somatic mutation, which suggests local microenvironmental factors in HD pathogenesis.


Assuntos
Síndrome de Down/epidemiologia , Doença de Hirschsprung/genética , Íntrons/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-ret/genética , Proto-Oncogenes , Grupo com Ancestrais do Continente Africano/genética , Causalidade , Comorbidade , Análise Mutacional de DNA , Europa (Continente)/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Doença de Hirschsprung/etnologia , Doença de Hirschsprung/patologia , Humanos , Lactente , Intestinos/patologia , Masculino , Polimorfismo de Fragmento de Restrição , África do Sul/epidemiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-22184102

RESUMO

BACKGROUND: Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon. Our previous results showed increased semaphorin 3A (SEMA3A) expression may be the risk factor for HSCR pathology in a subset of patients. Therefore, the association between polymorphisms in SEMA3A and the risk of HSCR was examined. METHODS: The genotypes of two SNPs (rs7804122 and rs797821) in the SEMA3A gene in 119 patients with HSCR and 93 controls were examined using PCR-sequencing to determine the contribution of SEMA3A to the HSCR phenotype. PCR reaction with cDNA template was also used to find out whether a novel mutation (Chr7:83634610A→T) influences the SEMA3A pre-mRNA splicing. RESULTS: Genotypes comprising allele G of rs7804122 (GG or AG) were over-represented in patients (48.74 vs. 24.8%; p = 0.0013) which indicated that the risk of HSCR was significantly higher among subjects with the GG or AG genotype than among the subjects with the AA genotype. No statistically significant associations were found for SNP rs797821 at the allele or genotype levels. The differences in genotypes and allele distributions of rs7804122 and rs797821 between various clinical classifications were not statistically significant. The novel heterozygous mutation (Chr7:83634610A→T) 30bp away from an intron/exon boundary, had no detectable effect on splicing efficiency. CONCLUSION: Our results for rs7804122 provided preliminary evidence that the SEMA3A gene is involved in the susceptibility to HSCR in the Northeastern Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Doença de Hirschsprung/genética , Polimorfismo de Nucleotídeo Único , Semaforina-3A/genética , China , Éxons/genética , Feminino , Frequência do Gene , Genótipo , Heterozigoto , Doença de Hirschsprung/etnologia , Humanos , Íntrons/genética , Masculino , Mutação
8.
Am J Hum Genet ; 87(1): 60-74, 2010 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-20598273

RESUMO

The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) that probably arose once within the intronic RET enhancer MCS+9.7. With in vitro assays, we now show that the T variant disrupts a SOX10 binding site within MCS+9.7 that compromises RET transactivation. The T allele, with a control frequency of 20%-30%/47% and case frequency of 54%-62%/88% in European/Chinese-ancestry individuals, is involved in all forms of HSCR. It is marginally associated with proband gender (p = 0.13) and significantly so with length of aganglionosis (p = 7.6 x 10(-5)) and familiality (p = 6.2 x 10(-4)). The enhancer variant is more frequent in the common forms of male, short-segment, and simplex families whereas multiple, rare, coding mutations are the norm in the less common and more severe forms of female, long-segment, and multiplex families. The T variant also increases penetrance in patients with rare RET coding mutations. Thus, both rare and common mutations, individually and together, make contributions to the risk of HSCR. The distribution of RET variants in diverse HSCR patients suggests a "cellular-recessive" genetic model where both RET alleles' function is compromised. The RET allelic series, and its genotype-phenotype correlations, shows that success in variant identification in complex disorders may strongly depend on which patients are studied.


Assuntos
Doença de Hirschsprung/genética , Proteínas Proto-Oncogênicas c-ret/genética , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Estudos de Casos e Controles , Elementos Facilitadores Genéticos , Grupo com Ancestrais do Continente Europeu , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Haplótipos , Doença de Hirschsprung/etnologia , Doença de Hirschsprung/fisiopatologia , Humanos , Masculino , Mutação , Penetrância , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Proteínas Proto-Oncogênicas c-ret/metabolismo , Fatores de Transcrição SOXE/metabolismo , Fatores Sexuais , Ativação Transcricional
9.
PLoS One ; 5(6): e10918, 2010 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-20532249

RESUMO

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital disorder associated with the lack of intramural ganglion cells in the myenteric and sub-mucosal plexuses along varying segments of the gastrointestinal tract. The RET gene is the major gene implicated in this gastrointestinal disease. A highly recurrent mutation in RET (RET(R114H)) has recently been identified in approximately 6-7% of the Chinese HSCR patients which, to date, has not been found in Caucasian patients or controls nor in Chinese controls. Due to the high frequency of RET(R114H) in this population, we sought to investigate whether this mutation may be a founder HSCR mutation in the Chinese population. METHODOLOGY AND PRINCIPAL FINDINGS: To test whether all RET(R114) were originated from a single mutational event, we predicted the approximate age of RET(R114H) by applying a Bayesian method to RET SNPs genotyped in 430 Chinese HSCR patients (of whom 25 individuals had the mutation) to be between 4-23 generations old depending on growth rate. We reasoned that if RET(R114H) was a founder mutation then those with the mutation would share a haplotype on which the mutation resides. Including SNPs spanning 509.31 kb across RET from a recently obtained 500 K genome-wide dataset for a subset of 181 patients (14 RET(R114H) patients), we applied haplotype estimation methods to determine whether there were any segments shared between patients with RET(R114H) that are not present in those without the mutation or controls. Analysis yielded a 250.2 kb (51 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients. CONCLUSIONS: This suggests that RET(R114H) is a founder mutation for HSCR in the Chinese population.


Assuntos
Efeito Fundador , Haplótipos , Doença de Hirschsprung/genética , Mutação , Proteínas Proto-Oncogênicas c-ret/genética , Estudos de Casos e Controles , China , Doença de Hirschsprung/etnologia , Humanos , Polimorfismo de Nucleotídeo Único
10.
J Pediatr Surg ; 44(9): 1805-11, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19735829

RESUMO

BACKGROUND: Hirschsprung disease (HSCR, OMIM 142623) is a complex congenital disorder characterized by intestinal obstructions caused by the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. The PHOX2B gene is involved in neurogenesis and disruption of Phox2b in mice results in a HSCR-like phenotype. The first association study of the PHOX2B gene with HSCR derived from Chinese population in Hong Kong; here, we address the question of whether PHOX2B acts as a predisposing factor in HSCR pathogenesis in Chinese population in mainland. METHODS: To investigate the contribution of PHOX2B to the HSCR phenotype, polymerase chain reaction amplification and direct sequencing were used to screen PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 102 patients with HSCR and 96 ethnically matched controls, in Han Chinese populations of Southeastern China. RESULTS: In this study, we genotyped 4 single nucleotide polymorphisms (SNPs) (including 1 novel SNP) located within the PHOX2B gene. Statistically significant differences were found for c.701 A > G and IVS2 + 100 A > G, and the log-additive model was accepted as the best inheritance model (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.11-2.87) for IVS2 + 100 A > G. We also showed that the haplotype-A G A N composed of 4 SNPs exhibited significant association with the disease (P = .03); this haplotype was more frequently observed in cases than in controls (OR, 2.31; 95% CI, 1.11-4.82). CONCLUSIONS: Our study provided further evidence that the PHOX2B gene is involved in the susceptibility to HSCR in the Han Chinese population. Our findings are in accordance with the involvement of PHOX2B in the signaling pathways governing the development of enteric neurons.


Assuntos
Doença de Hirschsprung/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Distribuição de Qui-Quadrado , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Doença de Hirschsprung/epidemiologia , Doença de Hirschsprung/etnologia , Hong Kong/epidemiologia , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 9(2): 152-6, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16555159

RESUMO

OBJECTIVE: To establish the genetic background of exon2, exon13, exon11 and exon15 polymorphisms of RET proto-oncogene and study the possible involvement of RET proto-oncogene in the etiology of Hirschsprung disease (HD) in Chinese Han population surrounding Province HuBei. METHODS: The genotype and allele frequencies of RET proto-oncogene polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPS) in 94 HD patients and 122 control subjects. RESULTS: The genotype and allele frequencies of exon2 were AA 0.17, AG 0.72, GG 0.11, A 0.53, G 0.47 in control, and AA 0.61, AG 0.35, GG 0.04, A 0.78, G 0.22 in HD, and those of exon13 were GG 0.30, GT 0.52, TT 0.18, G 0.56, T 0.44 in control, and GG 0.49, GT 0.36, TT 0.15, G 0.67, T 0.33 in HD. There were significant differences in the two polymorphisms above between HD and control. The genotype and allele frequencies of exon11 were AA 0.05, AG 0.16, GG 0.79, A 0.13, G 0.87 in control and AA 0.02, AG 0.14, GG 0.84, A 0.09, G 0.91 in HD, the differences were not found between these two groups about this site. Exon15 were all of CC genotype in spite of control or HD. CONCLUSIONS: These data provide evidences for the contributions of exon2 and exon13 polymorphisms of RET proto-oncogene to susceptibility to HD in Chinese Han population surrounding province.


Assuntos
Doença de Hirschsprung/etnologia , Doença de Hirschsprung/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas c-ret/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Pré-Escolar , China , Éxons , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino
12.
Hawaii Med J ; 64(4): 96-8, 100-1, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15921246

RESUMO

INTRODUCTION: Tripler Army Medical Center (TAMC) in Honolulu, Hawaii, is uniquely situated to serve patients from the United States Associated Pacific Islands (USAPIs) through the congressionally funded Pacific Island Health Care Project (PIHCP). Because of time differences and distance, a web-based store-and-forward consultation and referral network was established using the internet to more efficiently and economically facilitate patient care. Using both electronic and hard copy records, we sought to establish the incidence of Hirschsprung Disease (HD) in children from the USAPI and contrast it to that of the developed world. METHODS: PIHCP website records as well as all the inpatient and outpatient medical records of patients referred to TAMC fortreatment of HD from 1994 to 2002 were reviewed. A diagnosis of HD was confirmed in all cases with full thickness biopsy. Incidence figures for HD are based on this review and on the birth rates for these islands from the International Data Base of the U.S. Bureau of the Census. RESULTS: There were 14 cases of short-segment HD referred over a nine year study period. Nine patients came from the Federated States of Micronesia (FSM) with an average annual incidence of 1:3190, which is 1.5 to 2 times the reported incidence in Western nations. Remarkably, seven of these nine were from Pohnpei State, capital of the FSM (annual incidence of 1:1370 or3-5 times that in the West). Three patients came from the Republic of the Marshall Islands (RMI), and two came from American Samoa (AS). There were no reported consanguineous marriages, associated syndromes, or complications of surgery. CONCLUSION: HD was found to be up to 2-3 times more common among people from the FSM than has been reported in the developed world. Given the limitations of providing care and obtaining data from all the USAPls with a population that is spread over a massive expanse of ocean larger than the continental United States, this incidence is likely an underestimation of HD among Pacific Islanders. A secure web-based referral network developed in 1998 has been invaluable in collecting epidemiologic data from these islands as well as in providing health care workers in the USAPI with an efficient and inexpensive means to seek consultation from specialists and sub-specialists at a major tertiary care medical facility.


Assuntos
Doença de Hirschsprung/epidemiologia , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Doença de Hirschsprung/etnologia , Humanos , Incidência , Estudos Retrospectivos , Estados Unidos/epidemiologia
14.
Eur J Hum Genet ; 9(6): 419-23, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11436122

RESUMO

Hirschsprung's disease (HSCR) is a common cause of intestinal obstruction in neonates with an incidence of one in 5000 live births. The disease occurs due to the absence of parasympathetic neuronal ganglia in the hindgut, resulting in irregular or sustained contraction of the affected segment. DNA samples of 40 unrelated subjects with HSCR were subjected to mutation screening of the RET (REarranged during Transfection) proto-oncogene, the major susceptibility gene for HSCR. Five novel (V202M, E480K, IVS10-2A/G, D771N, IVS19-9C/T) and one previously described mutation (P973L) were identified. Only two of the mutation-positive patients (from different ethnic groups) displayed total colonic aganglionosis, and both were heterozygous for mutation D771N. The potential disease-causing mutations occurred in 20% of individuals, with more males (22.5% representing seven of 31 males) affected than females (12.5% representing one of eight females). This study represents the first comprehensive genetic analysis of this disease in the diverse South African population.


Assuntos
Proteínas de Drosophila , Doença de Hirschsprung/genética , Mutação , Grupo com Ancestrais do Continente Africano , Análise Mutacional de DNA , Grupo com Ancestrais do Continente Europeu , Éxons , Feminino , Haplótipos , Heterozigoto , Doença de Hirschsprung/etnologia , Humanos , Íntrons , Masculino , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases , Fatores Sexuais , África do Sul
15.
Harefuah ; 127(5-6): 148-54, 216, 1994 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-7995580

RESUMO

We treated 65 children with proven Hirschprung's disease between 1970-1992. After definitive surgery, 35 were over 10 years of age and 13 were over 18. The male:female ratio was 4:1. All but 3 were born full-term. 44% were of Bedouin origin, with a higher prevalence in 3 families of 2 tribes. 38 (58%) were diagnosed in the neonatal period: by barium enema and rectal muscle biopsy in 42 (65%), and by barium enema alone in 23 (35%). In the latter the diagnosis was verified by intra-operative biopsy. Severe constipation, intestinal obstruction or enterocolitis were the presenting features. 19 associated anomalies were found in 12 children, but none was life-threatening; 5 (8%) had cardiac anomalies; none had Down's syndrome. The rectosigmoid colon was the most common aganglionic segment involved (only 1 had total colonic aganglionosis). 7 of the 8 with short segment involvement responded well to posterior rectal myectomy. 55 patients had an abdominoperineal pull-through: 48 by Swenson's procedure and 5 by the Soave and 2 by the Duhamel modifications. In 43 a protective colostomy was performed at the end of the procedure. 53 had complete diversion colostomy at the time of initial diagnosis (neonatal and early infancy). There was no intra- or immediate post-operative death. 1 patient died 2 months after operation of complications following enterocolitis and total parenteral nutrition. 2 died a few hours after admission of severe sepsis due to enterocolitis before operation was possible. There were early postoperative complications in 11% of the 151 operations, mostly minor wound infections.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Doença de Hirschsprung , Adolescente , Criança , Colostomia , Grupos Étnicos , Feminino , Seguimentos , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/etnologia , Doença de Hirschsprung/cirurgia , Humanos , Recém-Nascido , Israel/epidemiologia , Masculino , Complicações Pós-Operatórias/epidemiologia
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