title: Recurrent duplications of 17q12 associated with variable phenotypes.
abstract: The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Elyse
authors.initials: E
authors.lastname: Mitchell
authors.affiliation: Princess Anne Hospital, Wessex Clinical Genetics Service, Southhampton, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Douglas
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kjaegaard
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Callewaert
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanlander
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Multicare Health System, Genomics Institute, Tacoma, Washington.
authors.forename: Amy Lawson
authors.initials: AL
authors.lastname: Yuen
authors.affiliation: J.C. Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Cindy
authors.initials: C
authors.lastname: Skinner
authors.affiliation: IRCCS Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Pinella
authors.initials: P
authors.lastname: Failla
authors.affiliation: IRCCS Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Alberti
authors.affiliation: IRCCS Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Avola
authors.affiliation: IRCCS Associazione Oasi Maria Santissima, Troina, Italy.|Medical Genetics, University of Catania, Catania, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
authors.affiliation: University Hospital of Odense, Odense, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Kibaek
authors.affiliation: Department of Medical Genetics, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Digilio
authors.affiliation: Division of Pediatric Genetics, Metabolism and Genomic Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Hannibal
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nicolette S
authors.initials: NS
authors.lastname: den Hollander
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bizzarri
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Tomas
authors.initials: T
authors.lastname: Fitzgerald
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Serena
authors.initials: S
authors.lastname: Piazzolla
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Elke
authors.initials: E
authors.lastname: van Oudenhove
authors.affiliation: IRCCS Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.affiliation: J.C. Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Charles
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington.
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: Department of Pediatrics, University of California, San Francisco, California.
authors.forename: Anne
authors.initials: A
authors.lastname: Slavotinek
authors.affiliation: Payton Manning Children's Hospital, Indianapolis, Indiana.
authors.forename: Luis
authors.initials: L
authors.lastname: Escobar
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Rajan
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Crolla
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Carter
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.|Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jennelle C
authors.initials: JC
authors.lastname: Hodge
authors.affiliation: Division of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, Washington.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Mefford
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D058674:Chromosome Duplication; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics; D010641:Phenotype; D055815:Young Adult
keywords: CNV; duplication; genotype phenotype