title: Two familial microduplications of 15q26.3 causing overgrowth and variable intellectual disability with normal copy number of IGF1R.
abstract: Terminal duplications of 15q26.3 are associated with an overgrowth phenotype, distinct facial features and intellectual disability, with the smallest reported microduplication to date being 3.16 Mb in size. We report two familial 15q26.3 microduplication cases that are less than half this size, re-defining the minimal critical region for this duplication syndrome. In both families the duplication (albeit a complex copy number gain in one family) is associated with tall stature, early speech delay and variable cognitive problems. Neither familial copy number gains encompass the gene encoding for the insulin-like growth factor 1 receptor (IGF1R), the most-cited candidate for the overgrowth phenotype. In one family, whole genome sequence data and break point mapping excludes disruption of known IGF1R regulatory elements due to potential insertion within these elements. These cases highlight the possibility that the distal region of 15q contains another gene regulating human growth, with LRRK1 being a potential candidate.
authors.affiliation: Genetics of Learning Disability Service, Hunter Genetics, Waratah, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Leffler
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Sanna
authors.initials: S
authors.lastname: Puusepp
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Olga
authors.initials: O
authors.lastname: Žilina
authors.affiliation: Genetics of Learning Disability Service, Hunter Genetics, Waratah, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Kati
authors.initials: K
authors.lastname: Kuuse
authors.affiliation: Department of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bain
authors.affiliation: Victorian Clinical Genetics Service, MCRI, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, Australia.
authors.forename: Trent
authors.initials: T
authors.lastname: Burgess
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Õunap
authors.affiliation: Genetics of Learning Disability Service, Hunter Genetics, Waratah, Australia. Electronic address: Mike.field@health.nsw.gov.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Field
mesh_terms: D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D006130:Growth Disorders / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D017526:Receptor, IGF Type 1; C510751:LRRK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Chromosome 15q26.3; Intellectual disability; Microduplication syndrome; Postnatal overgrowth