Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1

Wenke Seifert, Muriel Holder-Espinasse, Jirko Kühnisch, Kimia Kahrizi, Andreas Tzschach, Masoud Garshasbi, Hossein Najmabadi, Andreas Walter Kuss, Wolfram Kress, Geneviève Laureys, Bart Loeys, Eva Brilstra, Grazia M S Mancini, Hélène Dollfus, Karin Dahan, Kira Apse, Hans Christian Hennies, Denise Horn

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

LanguageEnglish
PagesE404-E420
Number of pages17
JournalHuman Mutation
Volume30
Issue number2
Early online date12 Nov 2008
DOIs
Publication statusPublished - Feb 2009
Externally publishedYes

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Mutation
Exons
Microcephaly
Frameshift Mutation
Retinitis Pigmentosa
Nonsense Codon
Myopia
Alternative Splicing
Neutropenia
Codon
Intellectual Disability
Retina
Cohen syndrome
Brain

Cite this

Seifert, W., Holder-Espinasse, M., Kühnisch, J., Kahrizi, K., Tzschach, A., Garshasbi, M., ... Horn, D. (2009). Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1. Human Mutation, 30(2), E404-E420. https://doi.org/10.1002/humu.20886
Seifert, Wenke ; Holder-Espinasse, Muriel ; Kühnisch, Jirko ; Kahrizi, Kimia ; Tzschach, Andreas ; Garshasbi, Masoud ; Najmabadi, Hossein ; Walter Kuss, Andreas ; Kress, Wolfram ; Laureys, Geneviève ; Loeys, Bart ; Brilstra, Eva ; Mancini, Grazia M S ; Dollfus, Hélène ; Dahan, Karin ; Apse, Kira ; Hennies, Hans Christian ; Horn, Denise. / Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1. In: Human Mutation. 2009 ; Vol. 30, No. 2. pp. E404-E420.
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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.",
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Seifert, W, Holder-Espinasse, M, Kühnisch, J, Kahrizi, K, Tzschach, A, Garshasbi, M, Najmabadi, H, Walter Kuss, A, Kress, W, Laureys, G, Loeys, B, Brilstra, E, Mancini, GMS, Dollfus, H, Dahan, K, Apse, K, Hennies, HC & Horn, D 2009, 'Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1', Human Mutation, vol. 30, no. 2, pp. E404-E420. https://doi.org/10.1002/humu.20886

Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1. / Seifert, Wenke; Holder-Espinasse, Muriel; Kühnisch, Jirko; Kahrizi, Kimia; Tzschach, Andreas; Garshasbi, Masoud; Najmabadi, Hossein; Walter Kuss, Andreas; Kress, Wolfram; Laureys, Geneviève; Loeys, Bart; Brilstra, Eva; Mancini, Grazia M S; Dollfus, Hélène; Dahan, Karin; Apse, Kira; Hennies, Hans Christian; Horn, Denise.

In: Human Mutation, Vol. 30, No. 2, 02.2009, p. E404-E420.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1

AU - Seifert, Wenke

AU - Holder-Espinasse, Muriel

AU - Kühnisch, Jirko

AU - Kahrizi, Kimia

AU - Tzschach, Andreas

AU - Garshasbi, Masoud

AU - Najmabadi, Hossein

AU - Walter Kuss, Andreas

AU - Kress, Wolfram

AU - Laureys, Geneviève

AU - Loeys, Bart

AU - Brilstra, Eva

AU - Mancini, Grazia M S

AU - Dollfus, Hélène

AU - Dahan, Karin

AU - Apse, Kira

AU - Hennies, Hans Christian

AU - Horn, Denise

N1 - (c) 2008 Wiley-Liss, Inc.

PY - 2009/2

Y1 - 2009/2

N2 - 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.

AB - 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.

KW - Abnormalities, Multiple

KW - Adolescent

KW - Adult

KW - Alternative Splicing

KW - Animals

KW - Base Sequence

KW - Child

KW - Child, Preschool

KW - DNA Mutational Analysis

KW - Exons

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Haplotypes

KW - Humans

KW - Infant

KW - Male

KW - Mice

KW - Middle Aged

KW - Molecular Sequence Data

KW - Pedigree

KW - Polymorphism, Genetic

KW - RNA Splice Sites

KW - RNA, Messenger

KW - Syndrome

KW - Vesicular Transport Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1002/humu.20886

M3 - Article

VL - 30

SP - E404-E420

JO - Human Mutation

T2 - Human Mutation

JF - Human Mutation

SN - 1059-7794

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Seifert W, Holder-Espinasse M, Kühnisch J, Kahrizi K, Tzschach A, Garshasbi M et al. Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1. Human Mutation. 2009 Feb;30(2):E404-E420. https://doi.org/10.1002/humu.20886