title: Familial intragenic duplication of ANKRD11 underlying three patients of KBG syndrome.
abstract: BACKGROUND
  KBG syndrome, a rare autosomal disorder characterised by distinctive craniofacial and skeletal features and developmental delay, is caused by haploinsufficiency of the ANKRD11 gene.
  
  
  RESULTS
  Here we describe two siblings with multiple symptoms characteristic of KBG and their mother with a milder phenotype. In the siblings, array-based comparative genomic hybridization (array CGH) identified an intragenic microduplication affecting ANKRD11 that was absent from the parents' array CGH profiles. Microsatellite analysis revealed the maternal origin of the rearrangement and interphase fluorescent in situ hybridization (i-FISH) experiments identified the rearrangement in low-level mosaicism in the mother. Molecular characterisation of the duplication allele demonstrated the presence of two mutant ANKRD11 transcripts containing a premature stop codon and predicting a truncated non-functional protein.
  
  
  CONCLUSIONS
  Similarly to deletions and point mutations, this novel pathogenetic rearrangement causes haploinsufficiency of ANKRD11, resulting in KBG syndrome.
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Crippa
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rusconi
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Castronovo
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy ; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Viotti 3/5, Milano, 20133 Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bestetti
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.affiliation: U.O.S Clinical Genetics and Pediatrics, MBBM Foundation San Gerardo Hospital, Via G. Pergolesi, 33, Monza, (MB) 20052 Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cereda
authors.affiliation: U.O.S Clinical Genetics and Pediatrics, MBBM Foundation San Gerardo Hospital, Via G. Pergolesi, 33, Monza, (MB) 20052 Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.affiliation: Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy ; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Viotti 3/5, Milano, 20133 Italy.
authors.forename: Palma
authors.initials: P
authors.lastname: Finelli
keywords: ANKRD11 intragenic duplication; Genotype–phenotype correlations; KBG syndrome; Low-level mosaicism
references.citation: Am J Hum Genet. 2014 Aug 7;95(2):173-82
references.pmid: 25087610
references.citation: Clin Genet. 1996 Oct;50(4):278-9
references.pmid: 9001820
references.citation: Am J Med Genet A. 2004 Dec 1;131(2):144-9
references.pmid: 15523620
references.citation: Birth Defects Orig Artic Ser. 1975;11(5):7-18
references.pmid: 1218237
references.citation: Am J Hum Genet. 2011 Aug 12;89(2):289-94
references.pmid: 21782149
references.citation: Am J Med Genet A. 2012 Mar;158A(3):547-52
references.pmid: 22307766
references.citation: Am J Med Genet A. 2013 May;161A(5):1073-7
references.pmid: 23463723
references.citation: Clin Dysmorphol. 2011 Jul;20(3):170-1
references.pmid: 21527850
references.citation: Eur J Hum Genet. 2012 Feb;20(2):131-3
references.pmid: 21654729
references.citation: Hum Genet. 2015 Feb;134(2):181-90
references.pmid: 25413698
references.citation: J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):353-61
references.pmid: 20601901
references.citation: Am J Med Genet A. 2014 Jul;164A(7):1744-9
references.pmid: 24838796
references.citation: Am J Med Genet A. 2013 Apr;161A(4):835-40
references.pmid: 23494856
references.citation: Eur J Med Genet. 2015 Feb;58(2):86-94
references.pmid: 25464108
references.citation: Ann Lab Med. 2014 Sep;34(5):390-4
references.pmid: 25187894
references.citation: Biochem Biophys Res Commun. 2007 Jul 13;358(4):1034-40
references.pmid: 17521611
references.citation: Orphanet J Rare Dis. 2006 Dec 12;1:50
references.pmid: 17163996
references.citation: Eur J Hum Genet. 2015 Sep;23(9):1176-85
references.pmid: 25424714
references.citation: Am J Med Genet A. 2007 Feb 1;143A(3):292-300
references.pmid: 17230487
references.citation: Genet Couns. 1998;9(3):191-4
references.pmid: 9777340