title: Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome.
abstract: Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen syndrome.
authors.affiliation: Gene Mapping Centre and Department of Molecular Genetics, Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.forename: Christian
authors.initials: C
authors.lastname: Schumi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Moser
authors.forename: Eva
authors.initials: E
authors.lastname: Al-Taji
authors.forename: Gholamali
authors.initials: G
authors.lastname: Tariverdian
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Anna
authors.initials: A
authors.lastname: Rajab
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Neumann
authors.forename: Katja M
authors.initials: KM
authors.lastname: Eckl
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karbasiyan
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
mesh_terms: D000015:Abnormalities, Multiple / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D002658:Developmental Disabilities / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008831:Microcephaly / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D013577:Syndrome; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins