Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome

• Published in: Journal of medical genetics 1997-09, Vol.34 (9), p.719-728
• Main Authors: Partington, M W, Fagan, K, Soubjaki, V, Turner, G
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; Chromosomes, Human, Pair 4; Complex syndromes; Diseases in Twins; Female; Gene Deletion; Genetic Markers; Growth Disorders - genetics; Humans; In Situ Hybridization, Fluorescence; Infant, Newborn; Intellectual Disability - genetics; Male; Medical genetics; Medical sciences; Middle Aged; Pedigree; Pregnancy; Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor - genetics; Translocation, Genetic
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.34.9.719

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.