title: 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.
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the degree of mental retardation, and short stature, the initially considered clinical diagnosis of Cohen syndrome was withdrawn and a novel genetic entity was assumed.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.
authors.affiliation: Institute of Human Genetics, Charité, Humboldt University, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Horn
authors.forename: A
authors.initials: A
authors.lastname: Krebsová
authors.forename: J
authors.initials: J
authors.lastname: Kunze
authors.forename: A
authors.initials: A
authors.lastname: Reis
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003241:Consanguinity; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006130:Growth Disorders; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability; D008126:Lod Score; D008297:Male; D008831:Microcephaly; D018895:Microsatellite Repeats; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D004247:DNA