High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome

Parri, Veronica; Katzaki, Eleni; Uliana, Vera; Scionti, Francesca; Tita, Rossella; Artuso, Rosangela; Longo, Ilaria; Boschloo, Renske; Vijzelaar, Raymon; Selicorni, Angelo; Brancati, Francesco; Dallapiccola, Bruno; Zelante, Leopoldo; Hamel, Christian; Sarda, Pierre; Lalani, Seema R.; Grasso, Rita; Buoni, Sabrina; Hayek, Joussef; Servais, Laurent; Vries, Bert B.A. de; Georgoudi, Nelly; Nakou, Sheena; Petersen, Michael B.; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

doi:10.1038/ejhg.2010.59

Cited by 32 publications

(32 citation statements)

References 17 publications

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“…In conclusion, here we describe 2 additional COH1 mutations leading to truncated or rapidly degraded alleles in agreement with the vast majority of COH1 alterations so far reported [Kolehmainen et al, 2004;Seifert et al, 2009;Parri et al, 2010]. …”

Section: Resultssupporting

confidence: 91%

Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome

et al. 2012

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Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697–9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband’s phenotype and improved the knowledge of genotype-phenotype correlation.

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Section: Resultssupporting

confidence: 91%

Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome

et al. 2012

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“…A variety of other studies have also reported a higher proportion of deletions among copy number mutations within single genes. 19,20 Several explanations may account for this observation. For example, carrying a complete extra copy of a gene is often not pathogenic.…”

Section: Discussionmentioning

confidence: 97%

Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders

Aradhya¹,

Lewis²,

Bonaga³

et al. 2012

Genetics in Medicine

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Purpose: Mendelian disorders are most commonly caused by mutations identifiable by DNA sequencing. Exonic deletions and duplications can go undetected by sequencing, and their frequency in most Mendelian disorders is unknown. methods:We designed an array comparative genomic hybridization (CGH) test with probes in exonic regions of 589 genes. Targeted testing was performed for 219 genes in 3,018 patients. We demonstrate for the first time the utility of exon-level array CGH in a large clinical cohort by testing for 136 autosomal dominant, 53 autosomal recessive, and 30 X-linked disorders.Results: Overall, 98 deletions and two duplications were identified in 53 genes, corresponding to a detection rate of 3.3%. Approximately 40% of positive findings were deletions of only one or two exons. A high frequency of deletions was observed for several autosomal dominant disorders, with a detection rate of 2.9%. For autosomal recessive disorders, array CGH was usually performed after a single mutation was identified by sequencing. Among 138 individuals tested for recessive disorders, 10.1% had intragenic deletions. For X-linked disorders, 3.5% of 313 patients carried a deletion or duplication.conclusion: Our results demonstrate that exon-level array CGH provides a robust option for intragenic copy number analysis and should routinely supplement sequence analysis for Mendelian disorders. 2012:14(6):594-603 Genet Med

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“…Mutations in COH1 are well established to cause autosomal recessive Cohen syndrome (4,5,(23)(24)(25); however, no study has addressed the biochemical characteristics or cellular localization and function of the encoded protein COH1 so far. We provide here by multiple lines of evidence that COH1 is a Golgiassociated protein that co-localizes with the cis-Golgi marker protein GM130.…”

Section: Discussionmentioning

confidence: 99%

Cohen Syndrome-associated Protein, COH1, Is a Novel, Giant Golgi Matrix Protein Required for Golgi Integrity

Seifert

Kühnisch

Maritzen

et al. 2011

Journal of Biological Chemistry

121

107

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High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome

Cited by 32 publications

References 17 publications

Two Novel <b><i>COH1</i></b> Mutations in an Italian Patient with Cohen Syndrome

Two Novel <b><i>COH1</i></b> Mutations in an Italian Patient with Cohen Syndrome

Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders

Cohen Syndrome-associated Protein, COH1, Is a Novel, Giant Golgi Matrix Protein Required for Golgi Integrity

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