Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1.
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.
Seifert
Wenke
W
Cologne Center for Genomics, University of Cologne, Germany.
Holder-Espinasse
Muriel
M
Kühnisch
Jirko
J
Kahrizi
Kimia
K
Tzschach
Andreas
A
Garshasbi
Masoud
M
Najmabadi
Hossein
H
Walter Kuss
Andreas
A
Kress
Wolfram
W
Laureys
Geneviève
G
Loeys
Bart
B
Brilstra
Eva
E
Mancini
Grazia M S
GM
Dollfus
Hélène
H
Dahan
Karin
K
Apse
Kira
K
Hennies
Hans Christian
HC
Horn
Denise
D
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
D022821:RNA Splice Sites; D012333:RNA, Messenger; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins