Disease relevance of VPS13B

• Cohen syndrome is an autosomal recessive disorder characterized by mental and motor retardation, short stature, microcephaly, several dysmorphic features, major ocular symptoms and granulocytopenia [1].
• Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia [2].
• Exclusion mapping of the Cohen syndrome gene from the Prader-Willi syndrome locus [3].
• Tapetoretinal degeneration in brothers with apparent Cohen syndrome: nosology with Mirhosseini-Holmes-Walton syndrome [4].
• Mutations in the Chediak-Higashi syndrome gene (CHS1) indicate requirement for the complete 3801 amino acid CHS protein [5].

Psychiatry related information on VPS13B

• Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy [6].
• Cognitive, language, and adaptive behavior profiles in individuals with a diagnosis of Cohen syndrome [7].
• Here, we report an 18-year-old male with Cohen syndrome associated with focal polymicrogyria and continuous spike-and-wave discharges during slow-wave sleep [8].
• The present investigation of 45 individuals with Cohen Syndrome (age 4-48 years) found that, although 57% of the sample were reported as showing some behavioural disturbance, problems related mainly to anxiety and social interactions; marked anti-social behaviours were rare [9].

High impact information on VPS13B

• Our results provide a tool to a more accurate definition of Cohen syndrome(s) and a starting point for the positional cloning of CHS1 [1].
• Cohen syndrome gene assigned to the long arm of chromosome 8 by linkage analysis [1].
• This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis [2].
• We have refined the critical region on chromosome 8q22 by haplotype analysis, and we report the characterization of a novel gene, COH1, that is mutated in patients with Cohen syndrome [10].
• Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport [10].

Chemical compound and disease context of VPS13B

• Monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified GBS components, including type III capsular polysaccharide (III-PS), group B antigen (GB-Ag), lipoteichoic acid (LTA), or Escherichia coli lipopolysaccharide [11].
• The Cohen syndrome. Retinal lesions and granulocytopenia [12].

Biological context of VPS13B

• Refined mapping of the Cohen syndrome gene by linkage disequilibrium [13].
• COH1-GT1 also shows decreased adherence to and invasion of respiratory epithelial cells in vitro and decreased virulence in vivo [14].
• We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation [15].
• Sexual development in a girl with Cohen syndrome [16].
• The response to UV-B- was most prominent in chs1 and almost silent in chs2, while the up-regulation by UV-B+ was most prominent in chs5 and chs6 and much less so in chs2 [17].

Anatomical context of VPS13B

• INTERPRETATION AND CONCLUSIONS: Neutrophil adhesive capability was greatly increased in a case of Cohen syndrome [18].
• In order to get insight into the mechanisms of neutropenia, we studied both the bone marrow and the functional properties of neutrophils obtained from peripheral blood (PB) or skin window (SW) exudate of a patient affected by Cohen syndrome [18].
• MRI of the brain in the Cohen syndrome: a relatively large corpus callosum in patients with mental retardation and microcephaly [19].
• The function of NK cells, CTL, and granulocytes is impaired by these mutations, indicating that polarized trafficking of vesicles is controlled by CHS1/beige proteins [20].
• Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG) [21].

Associations of VPS13B with chemical compounds

• A particulate fraction of a lysate of wild-type strain GBS COH1 mediated the transfer of galactose from UDP-galactose to an endogenous acceptor [22].
• Forty-five per cent of the input inoculum of COH1, a virulent GBS isolate, adhered to fibronectin immobilized on polystyrene [23].
• The specific biosynthetic defect in mutant strain COH1-11 was found to be in the activation of free sialic acid to CMP-sialic acid: CMP-sialic acid synthetase activity was present in the wild-type strain COH1 but was not detected in the asialo mutant strain COH1-11 [24].
• COH-1 infection of HUVE cells caused the release of lactate dehydrogenase activity [25].
• C3 fragments released by methylamine treatment of wild-type strain COH1 were predominantly in the form of C3bi, while those released from the acapsular mutant were predominantly C3b and those from the asialo mutant represented approximately equal amounts of C3b and C3bi [26].

Regulatory relationships of VPS13B

• Cohen syndrome with neutropenia-induced periodontitis managed with granulocyte colony-stimulating factor (G-CSF): case reports [27].

Other interactions of VPS13B

• Of the bacteria, only the Group B streptococcus COH-1 (GBS) induced release of TRAIL and concomittantly induced IFN-alpha [28].
• In five of these patients, a differential diagnosis was made (Ohdo-like blepharophimosis syndrome, Alstrøm syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypoparathyroidism) [29].
• Growth hormone deficiency in a girl with the Cohen syndrome [30].
• CONCLUSIONS: Progressive myopia and retinochoroidal dystrophy are essential features in Cohen syndrome and, together with early lens opacities, lead to deterioration of vision [31].
• The map will also be of interest to anyone trying to clone positionally disease genes in this region, such as Cohen syndrome (8q22-q23), Klip-Feil syndrome (8q22.2), hereditary spastic paraplegia (8q24), and benign adult familial myoclonic epilepsy (8q23.3-q24.1) [32].

Analytical, diagnostic and therapeutic context of VPS13B

• It shows similarities to Bardet-Biedl syndrome and Cohen syndrome, but can be distinguished by clinical features; the age of onset and nonprogressive nature of the visual impairment, the lack of characteristic facies, skin or gingival infection, microcephaly, 'mottled retina', polydactyly and small penis without testicular anomalies [33].
• Two fragments (approx. 600 bp; CHS1 and CHS2) were amplified from B. cinerea genomic DNA using degenerate PCR primers based on regions of complete amino acid homology between previously published chitin synthase gene sequences [34].
• Linkage mapping confirmed that CHS1, CHS3, CHS4, dCHS1, and the I locus are located at the same position in molecular linkage group (MLG) A2 [35].
• The administration of general anesthesia in patients with Cohen syndrome can be a challenge because most of these patients are mentally retarded and uncooperative and have facial malformations that may make intubation difficult [36].
• Two acridone synthase cDNAs (ACS1 and ACS2) have been cloned from Ruta cell cultures, and we report now the cloning of three chalcone synthase cDNAs (CHS1 to CHS3) from immature Ruta flowers [37].

References