Assuntos
Anormalidades Múltiplas/genética , Aneuploidia , Cromossomos Humanos Par 4/genética , Deficiência Intelectual/genética , Translocação Genética/genética , Adolescente , Criança , Pré-Escolar , Bandeamento Cromossômico , Quebra Cromossômica/genética , Humanos , Recém-Nascido , Cariotipagem , Masculino , Núcleo Familiar , Mapeamento Físico do Cromossomo , SíndromeRESUMO
Three families are reported who have a translocation involving 4p16.3. Nine subjects are described with the clinical features of the Pitt-Rogers-Danks (PRD) syndrome confirming pre- and postnatal growth failure, microcephaly, severe mental retardation, seizures, and a distinctive facial appearance; a deletion of 4p16.3 was seen in all eight patients studied with fluorescence in situ hybridisation (FISH). Eleven subjects had a new syndrome with physical overgrowth, heavy facial features, and mild to moderate mental handicap; a duplication of the chromosome region 4p16.3 was found in the four subjects studied. It is suggested that the growth abnormalities in these two families may be explained by a dosage effect of the fibroblast growth factor receptor gene 3 (FGFR3), which is located at 4p16.3, that is, a single dose leads to growth failure and a triple dose to physical overgrowth. We describe the molecular mapping of the translocation breakpoint and define it to within locus D4S43.