title: Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1.
abstract: Cohen syndrome is characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in COH1 (VPS13B) have been found in patients with Cohen syndrome from diverse ethnic origins. We have carried out mutation analysis in twelve novel patients with Cohen syndrome from nine families. In this series, we have identified 13 different mutations in COH1, twelve of these are novel including six frameshift mutations, four nonsense mutations, two splice site mutations, and a one-codon deletion. Since different transcripts of COH1 have been reported previously, we have analysed the expression patterns of COH1 splice variants. The transcript variant NM_152564 including exon 28b showed ubiquitous expression in all examined human tissues. In contrast, human brain and retina showed differential splicing of exon 28 (NM_017890). Moreover, analysis of mouse tissues revealed ubiquitous expression of Coh1 homologous to human NM_152564 in all examined tissues but no prevalent alternative splicing.
authors.affiliation: Cologne Center for Genomics, University of Cologne, Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Jirko
authors.initials: J
authors.lastname: Kühnisch
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.forename: Andreas
authors.initials: A
authors.lastname: Walter Kuss
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
authors.forename: Eva
authors.initials: E
authors.lastname: Brilstra
authors.forename: Grazia M S
authors.initials: GM
authors.lastname: Mancini
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Karin
authors.initials: K
authors.lastname: Dahan
authors.forename: Kira
authors.initials: K
authors.lastname: Apse
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins