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 entity

Am J Med Genet. 2000 Jun 5;92(4):285-92.

Abstract

A syndrome of microcephaly, progressive postnatal growth deficiency, and mental retardation was observed in two brothers and their cousin from a multiply consanguineous kindred of Lebanese descent. Hypotonia, chorioretinal dystrophy, and myopia were also identified. The severity of the condition varied among the closely related patients. Because of absence of a distinctive facial appearance, the degree of mental retardation, and short stature, the initially considered clinical diagnosis of Cohen syndrome was withdrawn and a novel genetic entity was assumed. Homozygosity mapping in this family assigned the gene to a 26.8-cM region on the chromosome band 8q21.3 -22.1, between the microsatellites at D8S270 and D8S514. The maximum two-point LOD score was found for marker at D8S267 (Zmax=3.237 at Omax=0.00). Intriguingly enough, the identified gene region overlaps the refined gene region for Cohen syndrome (COH1) [Kolehmainen et al., 1997: Euro J Hum Genet 5:206-213]. This fact encourages the hypothesis that the described kindred segregates for a variant of Cohen syndrome and suggests a redefinition of its phenotype.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8 / genetics*
  • Consanguinity
  • DNA / chemistry
  • DNA / genetics
  • Family Health
  • Female
  • Genetic Linkage
  • Growth Disorders
  • Homozygote
  • Humans
  • Intellectual Disability
  • Lod Score
  • Male
  • Microcephaly
  • Microsatellite Repeats
  • Pedigree
  • Sequence Analysis, DNA
  • Syndrome

Substances

  • DNA