title: Cohen syndrome in the Ohio Amish.
abstract: We describe eight members from two large Amish kindreds who share a phenotype characterized by early-onset pigmentary retinopathy and myopia, global developmental delay and mental retardation, microcephaly, short stature, hypotonia, joint hyperextensibility, small hands and feet, common facial appearance, and friendly disposition. Several of the children had intermittent granulocytopenia. The phenotypic occurrence in three siblings coupled with the increased coefficient of inbreeding in the Amish suggested that this disorder is autosomal recessive and due to a single founder allele. Despite similarity to the clinical features of Cohen syndrome, experienced dysmorphologists attending the 23rd David W. Smith Workshop suggested the facial gestalt of the Amish children was inconsistent with this diagnosis. We mapped the locus responsible for these individuals' phenotype to chromosome 8q22-q23, which contains the recently discovered Cohen syndrome gene, COH1. Complete sequencing of the COH1 gene identified a likely disease-causing frameshift mutation and a missense mutation in the Amish patients. A comparison of features among different Cohen syndrome populations with shared linkage to the COH1 locus or known COH1 gene mutations may allow for the determination of improved clinical criteria on which to suspect the diagnosis of Cohen syndrome. We conclude that facial gestalt seems to be an unreliable indicator of Cohen syndrome between ethnic populations, although it is quite consistent among affected individuals within a particular ethnic group. Other features common to almost all individuals with proven COH1 mutations, such as retinal dystrophy, myopia, microcephaly, mental retardation, global developmental delay, hypotonia, and joint hyperextensibility appear to be better clinical indicators of this disorder.
authors.affiliation: Department of Pediatrics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA. marni.falk@uhhs.com
authors.forename: Marni J
authors.initials: MJ
authors.lastname: Falk
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Feiler
authors.forename: Derek E
authors.initials: DE
authors.lastname: Neilson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Maxwell
authors.forename: James V
authors.initials: JV
authors.lastname: Lee
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Segall
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Robin
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.forename: Ann-Liz
authors.initials: AL
authors.lastname: Träskelin
authors.forename: Juha
authors.initials: J
authors.lastname: Kolehmainen
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Max
authors.initials: M
authors.lastname: Wiznitzer
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D017668:Age of Onset; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D009123:Muscle Hypotonia / Q000235:genetics*; D009216:Myopia / Q000235:genetics; D009765:Obesity; D009820:Ohio; D010375:Pedigree; D010551:Personality; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics*; D035781:Siblings; D013577:Syndrome; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins