Hirschsprung's Disease: Genetic and Functional Associations of Down's and Waardenburg Syndromes

Moore, Samuel W.; Johnson, A. G.

doi:10.1016/s1055-8586(98)70011-3

Cited by 64 publications

(46 citation statements)

References 57 publications

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“…4 and 5). Despite a significantly increased risk for syndromic deafness in patients with HSCR (11,12), no effective therapies for deafness have been established. Therefore, our findings will be useful for the development of therapeutical strategies targeting c-RET kinase against hearing impairments.…”

Section: Discussionmentioning

confidence: 99%

“…c-RET has been shown to be essential for the development and maintenance of the enteric nervous system (ENS) in both mice and humans (8,9) and to be the most frequent causal gene of Hirschsprung disease (HSCR) in humans (20-25% of cases) (11,12). In fact, severe HSCR with total intestinal agangliosis has been shown to develop in homozygous knockin (KI) mice, in which Y1062 in c-Ret was replaced with phenylalanine (c-Ret-KI Y1062F/Y1062F mice) (6).…”

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confidence: 99%

“…A significantly increased risk for dominant sensorineural deafness in patients who have HSCR caused by endothelin receptor type B (EDNRB) (13) and SOX10 (14) has been reported (11,12). Despite the fact that c-RET is one of the responsible genes for HSCR, there is no direct evidence to link c-Ret and c-RET with deafness in mice and humans, presumably because of the short life span [postnatal day (P) 1-2)] of c-Ret homozygously deleted mice (15) to measure hearing levels.…”

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confidence: 99%

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c-Ret–mediated hearing loss in mice with Hirschsprung disease

Ohgami

Ida-Eto

Shimotake

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by endothelin receptor type B and SOX10 has been reported. Despite the fact that c-RET is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-Ret and c-RET cause congenital deafness in mice and humans. Here, we show that impaired phosphorylation of c-Ret at tyrosine 1062 causes HSCR-linked syndromic congenital deafness in c-Ret knockin (KI) mice. The deafness involves neurodegeneration of spiral ganglion neurons (SGNs) with not only impaired phosphorylation of Akt and NF-κB but decreased expression of calbindin D28k in inner ears. The congenital deafness involving neurodegeneration of SGNs in c-Ret KI mice was rescued by introducing constitutively activated RET. Taken together with our results for three patients with congenital deafness with c-RET-mediated severe HSCR, our results indicate that c-Ret and c-RET are a deafness-related molecule in mice and humans. spiral ganglion neuron | syndromic congenital deafness | tyrosine kinase A bout 30% of the 120 million people worldwide who suffer from congenital (early-onset) hearing loss are syndromic, and the remaining 70% are nonsyndromic (1-3). To elucidate the etiologies for the hearing losses, inner ears have been morphologically investigated as one of the target tissues. The inner ears contain the organ of Corti and the stria vascularis. The stria vascularis serves to maintain the endolymph potential. The organ of Corti, which consists of two kinds of sensory cells (inner hair cells and outer hair cells) is responsible for mechanotransduction, by which sound impulses are converted into neural impulses. Auditory information from the sensory cells is transmitted to spiral ganglion neurons (SGNs) as the primary carrier, followed by eventual transmission to the auditory cortex (1, 2

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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c-Ret–mediated hearing loss in mice with Hirschsprung disease

Ohgami

Ida-Eto

Shimotake

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Organik konstipasyonun genetik nedenleri arasında; inek sütü allerjisi, Hirschsprung hastalığı, kistik fibroz, hipotiroidi, anorektal malformasyonlar (anal fistül, anterior yerleşimli anal kanal gibi), çok düşük doğum ağırlığı, multipl endokrin neoplazi Tip 2 (MEN 2), intestinal psödo-obstrüksiyon sayı-labilir. 34,35 Otizmde de kabızlık daha sık karşımıza çıkmaktadır.…”

Section: B Konsti̇pasyonunclassified

Genetic Approach to Frequently Seen Pediatric Gastrointestinal System Diseases: Review

Ataman¹,

Erçal²

2016

Turkiye Klinikleri J Pediatr

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“…Both receptors are expressed on the epithelial cells forming the bud. Disruption of gdnf or of the genes coding for its two receptors blocked ureteric budding [59][60][61] . However, at least 20% of the gdnf −/− embryos formed a ureteric bud, indicating that factors other than GDNF participate in ureteric development.…”

Section: Growth Factors That Signal Via Tyrosine Kinasesmentioning

confidence: 99%

Branching Morphogenesis

Davies¹

2006

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Tubular structures are a fundamental anatomical theme recurring in a wide range of animal species. In mammals, tubulogenesis underscores the development of several systems and organs, including the vascular system, the lungs, and the kidneys. All tubular systems are hierarchical, branching into segments of gradually diminishing diameter. There are only two cell types that form the lumen of tubular systems -either endothelial cells in the vascular system, or epithelial cells in all other organs. The most important feature in determining the morphology of the tubular systems is the frequency and geometry of branching. Hence, deciphering the molecular mechanisms underlying the sprouting of new branches from pre-existing ones is the key to understanding the formation of tubular systems. The morphological similarity between the various tubular systems is underscored by similarities between the signaling pathways which control their branching. A prominent feature common to these pathways is their duality -an agonist counterbalanced by an inhibitor. The formation of the tracheal system in Drosophila melanogaster is driven by fibroblast growth factor (FGF) and inhibited by Sprouty/Notch. In vertebrates, the analogous pathways are FGF and transforming growth factor β in epithelial tubular systems, or vascular endothelial growth factor and Notch in the vascular system.

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Hirschsprung's Disease: Genetic and Functional Associations of Down's and Waardenburg Syndromes

Cited by 64 publications

References 57 publications

c-Ret–mediated hearing loss in mice with Hirschsprung disease

c-Ret–mediated hearing loss in mice with Hirschsprung disease

Genetic Approach to Frequently Seen Pediatric Gastrointestinal System Diseases: Review

Branching Morphogenesis

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