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
Cologne Center for Genomics, University of Cologne, Germany.
Hum Mutat. 2009 Feb;30(2):E404-20. doi: 10.1002/humu.20886.
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.
科恩综合征的特征为智力发育迟缓、出生后小头畸形、面部畸形、色素性视网膜病变、近视和间歇性中性粒细胞减少症。来自不同种族的科恩综合征患者中均发现了COH1(VPS13B)基因突变。我们对来自9个家庭的12例新发科恩综合征患者进行了突变分析。在这个系列研究中,我们在COH1中鉴定出13种不同的突变,其中12种是新发现的,包括6种移码突变、4种无义突变、2种剪接位点突变和1个密码子缺失。由于之前已报道过COH1的不同转录本,我们分析了COH1剪接变体的表达模式。包含外显子28b的转录变体NM_152564在所有检测的人体组织中均呈现普遍表达。相比之下,人脑和视网膜中外显子28(NM_017890)存在差异剪接。此外,对小鼠组织的分析显示,与人类NM_152564同源的Coh1在所有检测组织中均呈现普遍表达,但未发现明显的可变剪接。