CLMP Is Required for Intestinal Development, and Loss-of-Function Mutations Cause Congenital Short-Bowel Syndrome

Werf, Christine S. van der; Wabbersen, Tara D.; Hsiao, Nai-Hua; Paredes, Joana; Etchevers, Heather C.; Kroisel, Peter M.; Tibboel, Dick; Babarit, Candice; Schreiber, Richard A.; Hoffenberg, Edward J.; Vekemans, Michel; Zeder, Sirkka L.; Ceccherini, Isabella; Lyonnet, Stanislas; Ribeiro, Ana Sofia; Seruca, Raquel; Meerman, Gerard J. te; IJzendoorn, Sven C. D. van; Shepherd, Iain T.; Verheij, Joanne; Hofstra, Robert

doi:10.1053/j.gastro.2011.11.038

Cited by 53 publications

(91 citation statements)

References 16 publications

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“…50 cm compared with 250 cm). The latter condition is termed congenital SBS (CSBS) (Hasosah et al, 2008;van der Werf et al, 2015van der Werf et al, , 2012. In spite of the advances made in treatment options for SBS, the majority of CSBS patients die within the first year (Sabharwal et al, 2004;van der Werf et al, 2015).…”

Section: Short Bowel Syndromementioning

confidence: 99%

“…Mutations in two genes have been discovered to cause CSBS in humans (Table 2): CLMP and FLNA (van der Werf et al, 2015Werf et al, , 2012. CLMP encodes the Coxsackie-and adenovirus receptor-like membrane protein, a transmembrane protein that interacts with tight junctions.…”

Section: Short Bowel Syndromementioning

confidence: 99%

“…CLMP encodes the Coxsackie-and adenovirus receptor-like membrane protein, a transmembrane protein that interacts with tight junctions. The disease is inherited in an autosomal recessive manner and patients with CLMP mutations usually lack extra-intestinal symptoms (Van Der Werf et al, 2012). Overexpression of wild-type or mutant CLMP in human T84 cells (which do not normally express the protein) does not affect cell proliferation, migration, viability, or adhesion (van der Werf et al, 2013) and no mouse model has yet been generated for the Clmp mutation.…”

Section: Short Bowel Syndromementioning

confidence: 99%

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Generation of intestinal surface: an absorbing tale

et al. 2016

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The vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this extensive surface include generation of an extremely long tube and convolution of the absorptive surface of the tube into villi and microvilli. In this Review, we discuss recent findings regarding the morphogenetic and molecular processes required for intestinal tube elongation and surface convolution, examine shared and unique aspects of these processes in different species, relate these processes to known human maladies that compromise absorptive function and highlight important questions for future research.

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Section: Short Bowel Syndromementioning

confidence: 99%

Section: Short Bowel Syndromementioning

confidence: 99%

Section: Short Bowel Syndromementioning

confidence: 99%

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Generation of intestinal surface: an absorbing tale

et al. 2016

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“…15 In addition, Schalamon et al 16 observed an abnormal bowel wall with signs of neuronal intestinal dysplasia in a patient from a consanguineous Turkish family, in whom a truncating homozygous mutation in CLMP was detected. 6 In other cases, no abnormalities of the nerve plexus were observed on routine histology or by acetylcholinesterase staining. 17,18 However, histology specimens were not available for all cases.…”

Section: Discussionmentioning

confidence: 92%

“…The identification of homozygous and compound heterozygous mutations in Coxsackie-and adenovirus receptor-like membrane protein (CLMP) in CSBS patients confirmed an autosomal recessive pattern of inheritance in most affected families. 6 However, no CLMP mutations were identified in one Italian family 7,8 or in an isolated GermanAmerican male ( Table 1) who presented with congenital short bowel syndrome. 5 In the affected family, only males developed the disease, consistent with an X-linked pattern of inheritance (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations

Werf

Sribudiani

Verheij

et al. 2013

Genetics in Medicine

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Novel no‐stop FLNA mutation causes multi‐organ involvement in males

Oegema

Hulst

Theuns-Valks

et al. 2013

American J of Med Genetics Pt A

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Mutations in FLNA (Filamin A, OMIM 300017) cause X-linked periventricular nodular heterotopia (XL-PNH). XL-PNH-associated mutations are considered lethal in hemizygous males. However, a few males with unusual mutations (including distal truncating and hypomorphic missense mutations), and somatic mosaicism have been reported to survive past infancy. Two brothers had an atypical presentation with failure to thrive and distinct facial appearance including hypertelorism. Evaluations of these brothers and their affected cousin showed systemic involvement including severe intestinal malfunction, malrotation, congenital short bowel, PNH, pyloric stenosis, wandering spleen, patent ductus arteriosus, atrial septal defect, inguinal hernia, and vesicoureteral reflux. The unanticipated finding of PNH led to FLNA testing and subsequent identification of a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). Western blotting and qRT-PCR of patients' fibroblasts showed diminished levels of protein and mRNA. This FLNA mutation, the most distal reported so far, causes in females classical XL-PNH, but in males an unusual, multi-organ phenotype, providing a unique insight into the FLNA-associated phenotypes.

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CLMP Is Required for Intestinal Development, and Loss-of-Function Mutations Cause Congenital Short-Bowel Syndrome

Cited by 53 publications

References 16 publications

Generation of intestinal surface: an absorbing tale

Generation of intestinal surface: an absorbing tale

Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations

Novel no‐stop FLNA mutation causes multi‐organ involvement in males

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