Pathogenesis of Hirschsprung’s disease and its variants: recent progress

Puri, Prem; Shinkai, Toko

doi:10.1053/j.sempedsurg.2003.09.004

Cited by 65 publications

(52 citation statements)

References 88 publications

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“…One distinguishing feature that should be noticed in our patients was that six of seven mutations of RET belonged to the LSD group whereas mutations found in other genes were confined to cases with rectosigmoid extent. In agreement with other reports, cases harboring heterozygous mutation of EDNRB were mainly short segment HSCR who had unaffected parents or were asymptomatic (Amiel and Lyonnet 2001;Puri and Shinkai 2004;Tam and GarciaBarcelo 2004).…”

Section: Discussionsupporting

confidence: 79%

“…During the past decade, at least eight genes associated with the disease have been identified (reviewed by Puri 1997, 1998;Amiel and Lyonnet 2001;Puri and Shinkai 2004). Most candidate genes belong to two major signaling pathways which have essential roles in migration and maturation of an enteric neuroblast, RET transmembrane receptor system (RET, GDNF), and endothelin receptor system (EDNRB, ET-3).…”

Section: Introductionmentioning

confidence: 99%

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Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

et al. 2006

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Mutation and polymorphism data for Hirschsprung disease (HSCR) varies among ethnic groups. Single nucleotide polymorphisms (SNP) of RET protooncogene (RET) were recently shown to be associated with the disease, and with disease severity, in different populations. In this study, comprehensive analysis of RET, GDNF, EDNRB, ET-3, and SOX-10 genes among sporadic HSCR in Thailand was conducted by standard PCR-SSCP, RFLP, and sequencing methods. Of 41 patients, 30 cases had rectosigmoid disease (RSD) and 11 cases were assigned to the long-segment disease (LSD) group. Four missense mutations of RET, S100M, R231H, T278N, and G533S, were identified in three patients. One novel missense mutation, V111Q, was detected in EDNRB. For ET-3, two novel missense mutations, D166E and C173R, occurred concomitantly in a patient. The incidence of missense mutation was significantly higher in our female HSCR patient than in the male counterpart. Statistical analysis of the SNPs revealed a significant difference between allele distribution of RET L769L in patients in the LSD and RSD groups. The predominant genotype construct of RET A45A/L769L in our HSCR was GG/GG, which is obviously different from results from all previous studies. The GG/GG genotype construct was associated with RSD and with males. The study also detected a variant allele of RET S836S which has never been reported in Asian cohorts.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

et al. 2006

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“…The most studied are mutations in RET proto-oncogen, which is the major genetic cause of HSCR. The RET signaling pathway is of importance for enteric nervous system development to promote survival of neurons, mitosis of neuronal progenitor cells, differentiation of neurons and nerve fi bers extension (2,30). In the neighboring Czech Republic, the occurrence of RET mutation in patients with HSCR is estimated to be 10 % (31).…”

Section: Discussionmentioning

confidence: 99%

“…This mouse exhibits total intestinal agangliosis and renal agenesis (37,38). The mean reported incidence of RET proto-oncogen mutations is 70-80 % in cases of long-segment HSCR, 50 % in familial cases of HSCR and 15-20 % of sporadic forms of HSCR (30,39). It is highly probable, that patients with these mutations have higher susceptibility for developmental anomalies of kidney and excretory passages.…”

Section: Hirschsprung Disease and Genitourinary Malformationsmentioning

confidence: 99%

An embryological point of view on associated congenital anomalies of children with Hirschsprung disease

Slavikova¹,

Zabojnikova²,

J³

et al. 2015

BLL

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The most common congenital gut motility disorder is the Hirschsprung disease (HSCR). This anomaly is characterized by absence of neural crest-derived enteric neuronal ganglia. The aim of our study was to analyze the relationship between HSCR and other congenital anomalies or malfunctions. We examined 130 patients with Hirschsprung disease from Slovakia for last 10 years. During patients examination we focused not only on morphological abnormalities, but also functional anomalies. The incidence of associated congenital anomalies in our patients with HSCR was 26.1 %. But if we add functional defects (hypothyroidism, malfunction in cellular immunity, neurological defi cit) to the morphological congenital abnormalities, the rate of the patients with HSCR with additional defects achieves 50.1 %. Nine of our patients (6.9 %) had syndromic HSCR. The most frequent disorder (13.6 % of patients) was primary defi ciency in cellular immunity. More than 12.3 % of patients with HSCR had genitourinary abnormalities, in 10.0 % of patients variable degree of psychomotor retardation was observed, and skeletal, muscle and limb anomalies involved 7.7 % of patients. In 7.6 % cases of patients we found congenital hypothyroidism (including 2 cases of agenesis of thyroid gland). More than 6.1 % of patients presented with an associated anomaly in gastrointestinal tract (mostly anorectal malformations). Up to 5.5 % patients had congenital anomaly of heart, 3.8 % had ophthalmic and 3.1 % had craniofacial anomalies. Down syndrome was the main diagnosis in 3.8 % patients. We discussed the relationship between HSCR and other anomalies, which are probably caused by abnormal migration, proliferation, or differentiation, of neural crest cells during embryogenesis (Tab. 1, Fig. 2, Ref. 75). Text in PDF www.elis.sk.

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“…The aganglionic colon wall segment contains instead increased number of hypertrophied parasympathetic nerve trunks. Although intensively studied, the details of multifactorial pathogenesis of HD remain not clear [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Topography and morphometry of intestinal mast cells in children with Hirschsprung's disease.

Hermanowicz

Dębek²,

Dzienis-Koronkiewicz³

et al. 2008

Folia Histochem Cytobiol.

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Mast cells (MC) are source of many biological active compounds like cytokines, arachidonic acid derivates, proteoglicanes, prostaglandins, proteases, free oxygen radials, NGF, PAF and many more. The role of MC in pathogenesis of Hirschsprung's disease (HD) is not clear. Substances produced by MC may exert an important effect on embryology, growth, differentiation and regeneration of intestinal nervous system. Additionally, MC products modulate inflammation processes thus influencing on the clinical course of HD. Present study was established to evaluate the morphologic MC examination as a support of making diagnosis in HD. The MC topography and morphometry were evaluated in specimens collected from aganglionic colon of patients with diagnosed HD. The results were compared with corresponding data from normally innervated colon of patients suffering from constipation, and normal colon of children not presenting defecation problems. MC were visualized using indirect immunohistochemical method LSAB with mouse antibody against human tryptase. The MC visualized in submucosa and muscular layer in Hirschsprung's disease were significantly larger in comparison with control group (p<0.05). Also the number of MC/mm 2 in mucosa and lamina propria in HD was significantly elevated (p<0.05). However, the MC density in submucosa was also higher but it was not high statistically significant. In muscular layer and in serosa density of MC/mm 2 was not statistically significant. In the intestinal wall MC in aganglionic segment in Hirschsprung's disease are significantly activated comparing with normally innervated colon segments taken from the patients from other groups. This may confirm the role of MC both in pathogenesis of HD and in the reparation processes of bowel nervous system.

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Pathogenesis of Hirschsprung’s disease and its variants: recent progress

Cited by 65 publications

References 88 publications

Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

An embryological point of view on associated congenital anomalies of children with Hirschsprung disease

Topography and morphometry of intestinal mast cells in children with Hirschsprung's disease.

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