Cohen syndrome in the Ohio Amish
- 23 March 2004
- journal article
- case report
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 128A (1), 23-28
- https://doi.org/10.1002/ajmg.a.30033
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.This publication has 10 references indexed in Scilit:
- 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 TransportAmerican Journal of Human Genetics, 2003
- Diagnostic criteria, clinical characteristics, and natural history of Cohen syndromeJournal of Medical Genetics, 2003
- The ophthalmic findings in Cohen syndromeBritish Journal of Ophthalmology, 2002
- Does a Jewish type of Cohen syndrome truly exist?American Journal of Medical Genetics, 2002
- Cohen Syndrome: Essential features, natural history, and heterogeneityAmerican Journal of Medical Genetics, 2001
- Ophthalmologic findings in cohen syndrome: A long-term follow-upOphthalmology, 2000
- Homozygosity mapping in a family with microcephaly, mental retardation, and short stature to a Cohen syndrome region on 8q21.3 - 8q22.1: Redefining a clinical entityAmerican Journal of Medical Genetics, 2000
- Refined mapping of the Cohen syndrome gene by linkage disequilibrium.European Journal of Human Genetics, 1997
- Cohen syndrome gene assigned to the long arm of chromosome 8 by linkage analysisNature Genetics, 1994
- A new syndrome with hypotonia, obesity, mental deficiency, and facial, oral, ocular, and limb anomaliesThe Journal of Pediatrics, 1973