title: Assessment of copy number variations in 120 patients with Poland syndrome.
abstract: BACKGROUND
  Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown.
  
  
  METHODS
  To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients.
  
  
  RESULTS
  Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis.
  
  
  CONCLUSIONS
  A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance.
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
authors.forename: Carlotta Maria
authors.initials: CM
authors.lastname: Vaccari
authors.affiliation: Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
authors.affiliation: Pediatric Surgery Unit and Airway Team, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Torre
authors.affiliation: Department of Genetic Medicine and Development, Geneva University Medical School, Geneva, Switzerland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.affiliation: Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Divizia
authors.affiliation: Plastic and Reconstructive Surgery, Pediatric Surgery Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Romanini
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bossi
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Musante
authors.affiliation: Radiology Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Valle
authors.affiliation: Reconstructive Microsurgery and Hand Surgery Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Senes
authors.affiliation: Reconstructive Microsurgery and Hand Surgery Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Catena
authors.affiliation: Medical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Bedeschi
authors.affiliation: Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy.|Present Address: Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Anwar
authors.initials: A
authors.lastname: Baban
authors.affiliation: U.O.S.D. Epidemiology and Biostatistics, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calevo
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Acquaviva
authors.affiliation: Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.|Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy.|Medical Genetics Unit, Istituto Giannina Gaslini, via G. Gaslini 5, 16148, Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy. apuliti@unige.it.|Medical Genetics Unit, Istituto Giannina Gaslini, Genoa, Italy. apuliti@unige.it.|Medical Genetics Unit, Istituto Giannina Gaslini, via G. Gaslini 5, 16148, Genoa, Italy. apuliti@unige.it.
authors.forename: Aldamaria
authors.identifier: http://orcid.org/0000-0001-9310-6514
authors.initials: A
authors.lastname: Puliti
mesh_terms: D058674:Chromosome Duplication; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D008297:Male; D011045:Poland Syndrome / Q000235:genetics*; D017384:Sequence Deletion
keywords: Array comparative genomic hybridization; Chromosome deletion; Chromosome duplication; Congenital abnormalities; DNA copy number variation; Limb anomalies; Musculoskeletal diseases; Pectoralis muscles; Poland syndrome