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

A syndrome of microcephaly, progressive postnatal growth deficiency, and me ntal retardation was observed in two brothers and their cousin from a multi ply consanguineous kindred of Lebanese descent, Hypotonia, chorioretinal dy strophy, and myopia were also identified, The severity of the condition var ied among the closely related patients. Because of absence of a distinctive facial appearance, the degree of mental retardation, and short stature, th e initially considered clinical diagnosis of Cohen syndrome was withdrawn a nd a novel genetic entity was assumed, Homozygosity mapping in this family assigned the gene to a 26.8-cM region on the chromosome band 8q21.3-22.1, b etween 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). Intrigui ngly enough, the identified gene region overlaps the refined gene region fo r Cohen syndrome (COH1) [Kolehmainen et al,, 1997: Euro J Hum Genet 5:206-2 13]. This fact encourages the hypothesis that the described kindred segrega tes for a variant of Cohen syndrome and suggests a redefinition of its phen otype, Am. J, Med. Genet, 92:285-292, 2000, (C) 2000 Wiley-Liss, Inc.