Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport.
Cohen syndrome is an uncommon autosomal recessive disorder whose diagnosis is based on the clinical picture of nonprogressive psychomotor retardation and microcephaly, characteristic facial features, retinal dystrophy, and intermittent neutropenia. We have refined the critical region on chromosome 8q22 by haplotype analysis, and we report the characterization of a novel gene, COH1, that is mutated in patients with Cohen syndrome. The longest transcript (14,093 bp) is widely expressed and is transcribed from 62 exons that span a genomic region of approximately 864 kb. COH1 encodes a putative transmembrane protein of 4,022 amino acids, with a complex domain structure. Homology to the Saccharomyces cerevisiae VPS13 protein suggests a role for COH1 in vesicle-mediated sorting and transport of proteins within the cell.
Kolehmainen
Juha
J
Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
Black
Graeme C M
GC
Saarinen
Anne
A
Chandler
Kate
K
Clayton-Smith
Jill
J
Träskelin
Ann-Liz
AL
Perveen
Rahat
R
Kivitie-Kallio
Satu
S
Norio
Reijo
R
Warburg
Mette
M
Fryns
Jean-Pierre
JP
de la Chapelle
Albert
A
Lehesjoki
Anna-Elina
AE
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D002648:Child; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins