Allelic Heterogeneity in the COH1 Gene Explains Clinical Variability in Cohen Syndrome

Hans Christian Hennies, Anita Rauch, Wenke Seifert, Christian Schumi, Elisabeth Moser, Eva Al-Taji, Gholamali Tariverdian, Krystyna H. Chrzanowska, Malgorzata Krajewska-Walasek, Anna Rajab, Roberto Giugliani, Thomas E. Neumann, Katja M. Eckl, Mohsen Karbasiyan, André Reis, Denise Horn

Research output: Contribution to journalArticle

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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 svndrome.

LanguageEnglish
Pages138-145
Number of pages8
JournalAmerican Journal of Human Genetics
Volume75
Issue number1
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

Fingerprint

Genes
Microcephaly
Mutation
Myopia
Neutropenia
Oman
Lebanon
Joint Instability
Retinitis Pigmentosa
Nonsense Codon
Poland
Finland
Turkey
Intellectual Disability
Germany
Brazil
Cohen syndrome
Chromosomes

Cite this

Hennies, Hans Christian ; Rauch, Anita ; Seifert, Wenke ; Schumi, Christian ; Moser, Elisabeth ; Al-Taji, Eva ; Tariverdian, Gholamali ; Chrzanowska, Krystyna H. ; Krajewska-Walasek, Malgorzata ; Rajab, Anna ; Giugliani, Roberto ; Neumann, Thomas E. ; Eckl, Katja M. ; Karbasiyan, Mohsen ; Reis, André ; Horn, Denise. / Allelic Heterogeneity in the COH1 Gene Explains Clinical Variability in Cohen Syndrome. In: American Journal of Human Genetics. 2004 ; Vol. 75, No. 1. pp. 138-145.
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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 svndrome.",
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Hennies, HC, Rauch, A, Seifert, W, Schumi, C, Moser, E, Al-Taji, E, Tariverdian, G, Chrzanowska, KH, Krajewska-Walasek, M, Rajab, A, Giugliani, R, Neumann, TE, Eckl, KM, Karbasiyan, M, Reis, A & Horn, D 2004, 'Allelic Heterogeneity in the COH1 Gene Explains Clinical Variability in Cohen Syndrome', American Journal of Human Genetics, vol. 75, no. 1, pp. 138-145. https://doi.org/10.1086/422219

Allelic Heterogeneity in the COH1 Gene Explains Clinical Variability in Cohen Syndrome. / Hennies, Hans Christian; Rauch, Anita; Seifert, Wenke; Schumi, Christian; Moser, Elisabeth; Al-Taji, Eva; Tariverdian, Gholamali; Chrzanowska, Krystyna H.; Krajewska-Walasek, Malgorzata; Rajab, Anna; Giugliani, Roberto; Neumann, Thomas E.; Eckl, Katja M.; Karbasiyan, Mohsen; Reis, André; Horn, Denise.

In: American Journal of Human Genetics, Vol. 75, No. 1, 07.2004, p. 138-145.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allelic Heterogeneity in the COH1 Gene Explains Clinical Variability in Cohen Syndrome

AU - Hennies, Hans Christian

AU - Rauch, Anita

AU - Seifert, Wenke

AU - Schumi, Christian

AU - Moser, Elisabeth

AU - Al-Taji, Eva

AU - Tariverdian, Gholamali

AU - Chrzanowska, Krystyna H.

AU - Krajewska-Walasek, Malgorzata

AU - Rajab, Anna

AU - Giugliani, Roberto

AU - Neumann, Thomas E.

AU - Eckl, Katja M.

AU - Karbasiyan, Mohsen

AU - Reis, André

AU - Horn, Denise

PY - 2004/7

Y1 - 2004/7

N2 - 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 svndrome.

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DO - 10.1086/422219

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