Figure 5 - uploaded by Susanne Fransson
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Tentative model of the chromosome region 9p, 1.2 Mb duplication. The green arrow represents the genes that are duplicated and thus present in 3 copies instead of the normal 2 copies. They include e.g., a group of interferon genes and the tumour suppressor genes CDKN2A/CDKN2B. The blue arrow represents the disrupted FOCAD gene where the 3'-end is present in three copies while the 5'-end is present in normal two copies.
Source publication
Background: Intestinal degenerative neuropathy without extra-intestinal involvement occurs as familial forms (FIDN) but the genetics behind is unknown. We studied a Swedish family with autosomal dominant disease and several cases of chronic intestinal pseudo-obstruction (CIP).
Methods: We included 33 members of a family sharing a male ancestor. Chr...
Contexts in source publication
Context 1
... is not exactly clear which gene is responsible for the enteric neuropathy in this family. One possibility to be considered is a gene dose effect, i.e., the occurrence of a dose sensitive gene or genes ( Figure 5, middle panel). Among the 22 protein-coding genes within the duplication (Table 2), there are several interferon genes and also the cell cycle regulating gene CDKN2A (cyclin-dependent kinase inhibitor 2A) (Figure 4). ...
Context 2
... a duplication in Xq28 causing neuropathic CIP has been reported and proposed to be linked to the Filamin A (FLNA) gene [19]. It can at present not be excluded that one of the genes in the Ch9 region, within or outside the duplication ( Figure 4) is mutated and associated with the familial intestinal neuropathy described here ( Figure 5, lower panel). However, exome sequencing did not indicate any novel or deleterious alterations within coding sequence of the genes in the Ch9 region. ...
Context 3
... is not exactly clear which gene is responsible for the enteric neuropathy in this family. One possibility to be considered is a gene dose effect, i.e., the occurrence of a dose sensitive gene or genes ( Figure 5, middle panel). Among the 22 protein-coding genes within the duplication (Table 2), there are several interferon genes and also the cell cycle regulating gene CDKN2A (cyclin-dependent kinase inhibitor 2A) (Figure 4). ...
Context 4
... a duplication in Xq28 causing neuropathic CIP has been reported and proposed to be linked to the Filamin A (FLNA) gene [19]. It can at present not be excluded that one of the genes in the Ch9 region, within or outside the duplication ( Figure 4) is mutated and associated with the familial intestinal neuropathy described here ( Figure 5, lower panel). However, exome sequencing did not indicate any novel or deleterious alterations within coding sequence of the genes in the Ch9 region. ...
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Citations
Introduction:
Gastrointestinal (GI) motility disorders comprise a wide range of different diseases affecting the structural or functional integrity of the GI neuromusculature. Their clinical presentation and burden of disease depends on the predominant location and extent of gut involvement as well as the component of the gut neuromusculature affected.
Areas covered:
A comprehensive literature review was conducted using the PubMed and Medline databases to identify articles related to GI motility and functional disorders, published between 2016 and 2023. In this article, we highlight the current knowledge of molecular and genetic mechanisms underlying GI dysmotility, including disorders of gut-brain interaction, which involve both GI motor and sensory disturbance.
Expert opinion:
Although the pathophysiology and molecular mechanisms underlying many such disorders remain unclear, recent advances in the assessment of intestinal tissue samples, genetic testing with the application of 'omics' technologies and the use of animal models will provide better insights into disease pathogenesis as well as opportunities to improve therapy.
Hirschsprung disease (HSCR) and Paediatric Intestinal Pseudo-obstruction (PIPO) comprise two of the most recognized and severe disorders of gastrointestinal (GI) motility. HSCR is a developmental disorder of the enteric nervous system invariably affecting the large intestine, whereas the majority of PIPO conditions represent congenital disorders of one or more components of the neuromusculature and more diffusely affect the GI tract. Histopathology is deemed the gold standard for the diagnosis of HSCR and, arguably, of PIPO, but, other diagnostic modalities such as manometric and genetic studies have seen recent advances that may increase their utility. Especially for PIPO, management is multidisciplinary and best performed in specialist referral centres. Surgery remains the only viable treatment for HSCR and appears essential to optimize and sustain feeding and viability of intestinal function in PIPO patients. Novel therapies such as neural stem cell transplants show promise for the future.
