Chronic intestinal pseudo-obstruction

Antonucci, Alexandra; Fronzoni, L.; Cogliandro, L.; Cogliandro, Rosanna; Caputo, Carla; Giorgio, Roberto De; Pallotti, Federica; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

doi:10.3748/wjg.14.2953

Cited by 189 publications

(249 citation statements)

References 67 publications

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“…CIPO is a severe digestive syndrome characterized by intestinal dysmotility, resembling mechanical obstruction in the absence of any obstructive process. 32 Affected children generally present with recurrent episodes of abdominal pain, abdominal distension and inability to defecate, and require a long-term parenteral nutrition and/or a gastroenterostomy. The clinical course of CIPO is almost inevitably severe, owing to deteriorating bowel function and complications related to parenteral nutrition and surgery.…”

Section: Discussionmentioning

confidence: 99%

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function

et al. 2015

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Loss-of-function mutations in filamin A (FLNA) cause an X-linked dominant disorder with multiple organ involvement. Affected females present with periventricular nodular heterotopia (PVNH), cardiovascular complications, thrombocytopenia and EhlersDanlos syndrome. These mutations are typically lethal to males, and rare male survivors suffer from failure to thrive, PVNH, and severe cardiovascular and gastrointestinal complications. Here we report two surviving male siblings with a loss-of-function mutation in FLNA. They presented with multiple complications, including valvulopathy, intestinal malrotation and chronic intestinal pseudo-obstruction (CIPO). However, these siblings had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. Trio-based whole-exome sequencing revealed a 4-bp deletion in exon 40 that was predicted to cause a lethal premature protein truncation. However, molecular investigations revealed that the mutation induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses. This study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA.

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Section: Discussionmentioning

confidence: 99%

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function

et al. 2015

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“…The idiopathic form of inflammatory degenerative ENS neuropathy is unrelated to neoplasms, infectious conditions, or other known diseases [61][62][63][64][65][66]. On the other hand, the varicella-zoster virus (i.e., chickenpox) establishes latency in ENS neurons and can reactivate to lyse and kill the neurons within 48 h of infection [54,55,[67][68][69].…”

Section: Non-inflammatory Degenerative Neuropathymentioning

confidence: 99%

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Wood

2016

Dig Dis Sci

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“…6,7 A group among the visceral myopathies comprises the enteric visceral myopathies characterized predominantly by impaired gastrointestinal propulsion resulting in pain, distention, malabsorption and even death. 8,9 Reports on familial cases have indicated an autosomal dominant inheritance. 10,11 The clinical variability is extensive and a severe form is the megacystis-microcolonintestinal hypoperistalsis (MMIH; MIM: 249210) syndrome with prenatal or neonatal onset of gastrointestinal obstruction and bladder enlargement.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution

et al. 2015

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Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolonintestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.

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Chronic intestinal pseudo-obstruction

Cited by 189 publications

References 67 publications

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function

Enteric Nervous System: Neuropathic Gastrointestinal Motility

Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution

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