title: Heterogeneous growth patterns in carriers of chromosome 7p12.2 imbalances affecting GRB10.
abstract: Chromosomal duplications and deletions in 7p12.2 have been described in patients with growth disturbance phenotypes, that is, Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS). The region harbors the imprinted GRB10/Grb10 gene which has been postulated to belong to a major fetal growth pathway. Based on its genomic localization, its physiological function and its imprinting status, GRB10/Grb10 was considered as a candidate for growth disturbance disorders. However, based on case reports with imbalances of the GRB10 locus it has been suggested that the altered GRB10 copy number should be responsible for the aberrant growth phenotype rather than an altered imprinting status of the gene. We now report on a patient with an increased height and weight in his first years of life carrying a de-novo duplication (5.1 Mb) of paternal 7p12.2 material. The increased growth in this patient again contradicts the hypothesis that a gain of GRB10 copies leads to growth restriction. Indeed, it is necessary to compare the regions of imbalances in 7p12 and the affected genes in the different patients as other genes than GRB10 in 7p12 might cause these aberrant growth phenotypes.
authors.affiliation: Institute of Human Genetics, Aachen, Germany. teggermann@ukaachen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.forename: Matthias
authors.initials: M
authors.lastname: Begemann
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gogiel
authors.forename: María
authors.initials: M
authors.lastname: Palomares
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández
authors.forename: Rosario
authors.initials: R
authors.lastname: Cazorla
authors.forename: Sabrina
authors.initials: S
authors.lastname: Spengler
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaúr
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D002897:Chromosomes, Human, Pair 7; D055028:Comparative Genomic Hybridization; D019066:Facies; D051383:GRB10 Adaptor Protein / Q000235:genetics*; D020440:Gene Duplication; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype
chemical_list: D051383:GRB10 Adaptor Protein