Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.
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.
Kolehmainen
Juha
J
Folkhalsan Institute of Genetics, and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Wilkinson
Robert
R
Lehesjoki
Anna-Elina
AE
Chandler
Kate
K
Kivitie-Kallio
Satu
S
Clayton-Smith
Jill
J
Träskelin
Ann-Liz
AL
Waris
Laura
L
Saarinen
Anne
A
Khan
Jabbar
J
Gross-Tsur
Varda
V
Traboulsi
Elias I
EI
Warburg
Mette
M
Fryns
Jean-Pierre
JP
Norio
Reijo
R
Black
Graeme C  M
GC
Manson
Forbes D C
FD
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
D008565:Membrane Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins