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
Abstrakt
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the degree of mental retardation, and short stature, the initially considered clinical diagnosis of Cohen syndrome was withdrawn and a novel genetic entity was assumed, Homozygosity mapping in this family assigned the gene to a 26.8-cM region on the chromosome band 8q21.3-22.1, between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 (Z(max)=3.237 at O-max=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,