Congenital Short Bowel Syndrome: from clinical and genetic diagnosis to the molecular mechanisms involved in intestinal elongation

Werf, Christine S. van der; Halim, Danny; Verheij, Joanne; Alves, Maria M.; Hofstra, Robert M.W.

doi:10.1016/j.bbadis.2015.08.007

Cited by 32 publications

(28 citation statements)

References 88 publications

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“…Beyond the OPDSDs, FLNA variants have also been shown to cause XCVD, PVNH1 and PVNH4, childhood interstitial lung disease (ChILD), structural cardiac and aortic anomalies, thoracic aortic aneurysms (TAA), chronic intestinal pseudo-obstruction (CIPO), and congenital short bowel syndrome (CSBS) (Fig. 5a) [57,[59][60][61][62][63][64][65][66][67][68][69][70][71]. Typically, PVNH, XCVD, CIPO and CSBS are thought to be caused by LOF mutations while OPDSDs are caused by GOF FLNA mutations.…”

Section: Discussionmentioning

confidence: 99%

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene

et al. 2020

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Background: Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases. Methods: We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations. Results: We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin ) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19-21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1). Conclusions: FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

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Section: Discussionmentioning

confidence: 99%

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene

et al. 2020

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“…CSBS is a rare hereditary gastrointestinal disorder for which no cure is available. Patients with CSBS revealed a very short small intestine with a length of approximately 50 cm at birth while normal humans display a length of 190-280 cm and which is accompanied by intestinal malrotation (Alves et al, 2016;Hamilton et al, 1969;Van der Werf et al, 2015 .…”

Section: Mutations In the Human Clmp Gene Cause Congenital Short-bowementioning

confidence: 99%

Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease

Matthäus

Langhorst

Schütz

et al. 2017

Molecular and Cellular Neuroscience

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The immunoglobulin superfamily represents a diverse set of cell-cell contact proteins and includes well-studied members such as NCAM1, DSCAM, L1 or the contactins which are strongly expressed in the nervous system. In this review we put our focus on the biological function of a less understood subgroup of Ig-like proteins composed of CAR (coxsackievirus and adenovirus receptor), CLMP (CAR-like membrane protein) and BT-IgSF (brain and testis specific immunoglobulin superfamily). The CAR-related proteins are type I transmembrane proteins containing an N-terminal variable (V-type) and a membrane proximal constant (C2-type) Ig domain in their extracellular region which are implicated in homotypic adhesion. They are highly expressed during embryonic development in a variety of tissues including the nervous system whereby in adult stages the protein level of CAR and CLMP decreases, only BT-IgSF expression increases within age. CAR-related proteins are concentrated at specialized cell-cell communication sites such as gap or tight junctions and are present at the plasma membrane in larger protein complexes. Considerable progress has been made on the molecular structure and interactions of CAR while research on CLMP and BT-IgSF is at an early stage. Studies on mouse mutants revealed biological functions of CAR in the heart and for CLMP in the gastrointestinal and urogenital systems. Furthermore, CAR and BT-IgSF appear to regulate synaptic function in the hippocampus.

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“…It is also important to know, which part of the small bowel has been shortened in these patients, since different parts have different function and histology, as a result, the residual length determines the outcome of disease. 25,26 Neonates with short bowel usually present electrolyte deficiency, nutrient deficiency, weight loss, and osmotic diarrhea. The main cause of a short bowel in newborns is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…CSBS patients with loss of function mutations in FLNA presented multiple congenital abnormalities in addition to a shortened small bowel, while patients with a mutation in CLMP have phenotypes mostly limited to the intestinal failure. 26 These genes were observed in the recessive and Xlinked form of CSBS, respectively. In some cases, the small intestine in patients with CLMP mutations is longer and diagnosis is performed earlier in life in comparison to patients with FLNA mutations.…”

Section: Discussionmentioning

confidence: 99%

“…In some cases, the small intestine in patients with CLMP mutations is longer and diagnosis is performed earlier in life in comparison to patients with FLNA mutations. 26,29,30 Actin-binding domain of FLNA protein is located in the terminal region. A study showed that a deletion in its region could cause abnormal actin arrangement in the lymphoblastic cell line of a CSBS case.…”

Section: Discussionmentioning

confidence: 99%

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First Report of Congenital Short Bowel Syndrome in an Iranian Patient Caused by a Mutation in the CLMP Gene

et al. 2018

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Congenital short bowel syndrome (CSBS) is a rare congenital neonatal disorder. CSBS results from intestinal impairment during embryogenesis. Mutated CXADR-like membrane protein (CLMP) and Filamin A genes are involved in the cause of CSBS. In this study, due to our misdiagnosis, we had to perform whole exome sequencing on the patient, and also we implemented cosegregation analysis on his parents with consanguineous marriage and also parents' mothers. We identified a homozygous loss of function mutation in the CLMP gene in exon 5 (c.664C > T, p.R222X). Also, both parents and grandmothers of the proband were heterozygous for this mutation. Loss of function mutation in CLMP causes CSBS, leading to impaired intestinal development.

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Congenital Short Bowel Syndrome: from clinical and genetic diagnosis to the molecular mechanisms involved in intestinal elongation

Cited by 32 publications

References 88 publications

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene

Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease

First Report of Congenital Short Bowel Syndrome in an Iranian Patient Caused by a Mutation in the CLMP Gene

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