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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=3042546822&partnerID=8YFLogxK
U2 - 10.1086/422219
DO - 10.1086/422219
M3 - Article
C2 - 15154116
AN - SCOPUS:3042546822
VL - 75
SP - 138
EP - 145
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -