title: Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.
abstract: Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date. We found 22 different COH1 mutations, of which 19 are novel, in probands identified by our diagnostic criteria. In addition, we identified another three novel mutations in patients with incomplete clinical data. By contrast, no COH1 mutations were found in patients with a provisional diagnosis of Cohen syndrome who did not fulfill the diagnostic criteria ("Cohen-like" syndrome). This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis.
authors.affiliation: Folkhalsan Institute of Genetics, and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kolehmainen
authors.forename: Robert
authors.initials: R
authors.lastname: Wilkinson
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Kate
authors.initials: K
authors.lastname: Chandler
authors.forename: Satu
authors.initials: S
authors.lastname: Kivitie-Kallio
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Ann-Liz
authors.initials: AL
authors.lastname: Träskelin
authors.forename: Laura
authors.initials: L
authors.lastname: Waris
authors.forename: Anne
authors.initials: A
authors.lastname: Saarinen
authors.forename: Jabbar
authors.initials: J
authors.lastname: Khan
authors.forename: Varda
authors.initials: V
authors.lastname: Gross-Tsur
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Mette
authors.initials: M
authors.lastname: Warburg
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Reijo
authors.initials: R
authors.lastname: Norio
authors.forename: Graeme C  M
authors.initials: GC
authors.lastname: Black
authors.forename: Forbes D C
authors.initials: FD
authors.lastname: Manson
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins