Clinical features and long-term survival in chronic intestinal pseudo-obstruction and enteric dysmotility

Lindberg, Greger; Iwarzon, Marie; Törnblom, Hans

doi:10.1080/00365520902839642

Cited by 66 publications

(61 citation statements)

References 27 publications

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“…4–6 The severity of the clinical presentation and the limited understanding of the disorder contribute to poor quality of life and increased mortality. 2,4–7 In addition, there are no specific biochemical or molecular biomarkers of CIPO, hindering further a correct diagnosis. From a genetic perspective, most CIPO patients are sporadic, although X-linked, autosomal dominant and recessive forms have been identified with mutations in filamin A ( FLNA ) 8,9 , actin G2 ( ACTG2 ) 10 , thymidine phosphorylase ( TYMP ) 11 / polymerase gamma ( POLG1 ) 12 and more recently in SGOL1 .…”

Section: Introductionmentioning

confidence: 99%

Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction

et al. 2015

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Background & Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimicks a mechanical sub-occlusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and indentify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of mRNA and proteins were analyzed by quantitative reverse transcription PCR, immunoblot, and mobility shift assays. cDNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a MO). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a MO zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 is also overexpressed in sporadic CIPO in sera and gut biopsies. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and development of enteric neurons.

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Section: Introductionmentioning

confidence: 99%

Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction

et al. 2015

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“…Clinically, it may be difficult to differentiate between severe IBS and dysmotility disorders at the initial meeting. The latter are patients who need more advanced health care than IBS patients and should be cared for by specialists in gastroenterology [7,8]. Sometimes patients with dysmotility disorders are not correctly diagnosed for many years [7].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS)

et al. 2011

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BackgroundIrritable bowel syndrome (IBS) and gastrointestinal (GI) dysmotility disorders have a similar clinical picture, although dysmotility disorders require the attention of a specialist. Patients with primary Sjögren's syndrome (pSS) have also been described to suffer from IBS-like symptoms. No objective marker is available to distinguish between the patients. A visual analogue scale has been developed for IBS patients (VAS-IBS) to measure treatment response of GI symptoms and well-being in patients with IBS. The aim of the present study was to examine if VAS-IBS could be used to compare the degree of GI complaints in different patient populations, to get an objective marker to differentiate between the patients.MethodsThe VAS-IBS consists of 7 VAS scales, namely, abdominal pain, diarrhoea, constipation, bloating and flatulence, vomiting and nausea, psychological well-being and the intestinal symptoms' influence on daily life. Consecutive female patients suffering from IBS, dysmotility disorders and pSS were asked to complete the VAS-IBS questionnaire when visiting the out-patient clinics. In addition, a control population consisting of healthy female volunteers was included.ResultsHealthy volunteers had almost no GI symptoms, whereas all 3 patient groups expressed symptoms. There was no statistical significant difference between IBS and dysmotility in any of the scales besides vomiting and nausea (p = 0.044). Except for constipation, patients with pSS had less severe symptoms than the others.ConclusionThe VAS-IBS questionnaire could be used to assess the level of GI symptoms. However, VAS scores do not help the clinicians to differentiate between IBS and other dysmotility disturbances.

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“…3). SID is often secondary to neuropathic and/or myopathic systemic disease, such as diabetes, amyloidosis, scleroderma or a paraneoplastic syndrome, or it may be drug-induced, inherited, or idiopathic [28]. Symptoms of abdominal pain, distension and fullness, nausea and vomiting, constipation, or diarrhea and reflux-like dyspepsia, may be acute, recurrent, or chronic.…”

Section: Small Intestinal Dysmotilitymentioning

confidence: 97%

Endoscopy in the Diagnosis and Management of Motility Disorders

Kopelman

Triadafilopoulos

2011

Dig Dis Sci

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Clinical features and long-term survival in chronic intestinal pseudo-obstruction and enteric dysmotility

Abstract: CIP and ED differ with respect to severity of measurable physiological derangement, nutritional needs and long-term prognosis. Our findings indicate that CIP and ED are different entities that require different approaches to management.

Cited by 66 publications

References 27 publications

Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction

Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction

Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS)

Endoscopy in the Diagnosis and Management of Motility Disorders

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