Cohen syndrome in the Ohio Amish

Marni J. Falk, Heidi Feiler, Derek E. Neilson, Kathleen Maxwell, James V. Lee, Samantha K. Segall, Nathaniel H. Robin, Kirk C. Wilhelmsen, Ann Liz Träskelin, Juha Kolehmainen, Anna Elina Lehesjoki, Max Wiznitzer, Matthew L. Warman

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalAmerican Journal of Medical Genetics
Volume128 A
Issue number1
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Amish
Microcephaly
Muscle Hypotonia
Myopia
Intellectual Disability
Joints
Retinal Dystrophies
Genes
Phenotype
Frameshift Mutation
Mutation
Agranulocytosis
Retinitis Pigmentosa
Inbreeding
Missense Mutation
Ethnic Groups
Population
Foot
Siblings
Hand

Keywords

  • COH1
  • Retinitis pigmentosa

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Falk, M. J., Feiler, H., Neilson, D. E., Maxwell, K., Lee, J. V., Segall, S. K., ... Warman, M. L. (2004). Cohen syndrome in the Ohio Amish. American Journal of Medical Genetics, 128 A(1), 23-28.

Cohen syndrome in the Ohio Amish. / Falk, Marni J.; Feiler, Heidi; Neilson, Derek E.; Maxwell, Kathleen; Lee, James V.; Segall, Samantha K.; Robin, Nathaniel H.; Wilhelmsen, Kirk C.; Träskelin, Ann Liz; Kolehmainen, Juha; Lehesjoki, Anna Elina; Wiznitzer, Max; Warman, Matthew L.

In: American Journal of Medical Genetics, Vol. 128 A, No. 1, 01.07.2004, p. 23-28.

Research output: Contribution to journalArticle

Falk, MJ, Feiler, H, Neilson, DE, Maxwell, K, Lee, JV, Segall, SK, Robin, NH, Wilhelmsen, KC, Träskelin, AL, Kolehmainen, J, Lehesjoki, AE, Wiznitzer, M & Warman, ML 2004, 'Cohen syndrome in the Ohio Amish', American Journal of Medical Genetics, vol. 128 A, no. 1, pp. 23-28.
Falk MJ, Feiler H, Neilson DE, Maxwell K, Lee JV, Segall SK et al. Cohen syndrome in the Ohio Amish. American Journal of Medical Genetics. 2004 Jul 1;128 A(1):23-28.
Falk, Marni J. ; Feiler, Heidi ; Neilson, Derek E. ; Maxwell, Kathleen ; Lee, James V. ; Segall, Samantha K. ; Robin, Nathaniel H. ; Wilhelmsen, Kirk C. ; Träskelin, Ann Liz ; Kolehmainen, Juha ; Lehesjoki, Anna Elina ; Wiznitzer, Max ; Warman, Matthew L. / Cohen syndrome in the Ohio Amish. In: American Journal of Medical Genetics. 2004 ; Vol. 128 A, No. 1. pp. 23-28.
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