title: Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome.
abstract: BACKGROUND
  Floating-Harbor syndrome is a rare autosomal dominant short stature syndrome with retarded speech development, intellectual disability and dysmorphic facial features. Recently dominant mutations almost exclusively located in exon 34 of the Snf2-related CREBBP activator protein gene were identified to cause FHS.
  
  
  METHODS
  Here we report the genetic analysis of 5 patients fulfilling the diagnostic criteria of FHS obtained by Sanger sequencing. All of them presented with short stature, speech delay as well as psychomotor delay and typical facial dysmorphism. Three patients showed a good response to growth hormone treatment.
  
  
  RESULTS
  Two patients demonstrate novel, heterozygous de novo frameshift mutations in exon 34 (c.7396delA and c.7218dupT) leading to premature stop mutations in SRCAP (p.Val2466Tyrfs*9 and p.Gln2407Serfs*36, respectively). In two further patients we found already known SRCAP mutations in exon 34, c.7330C > T and c.7303C > T, respectively, which also lead to premature stop codons: p.Arg2444* and p.Arg2435*. In one patient, we identified a novel de novo stop mutation in exon 33 (c.6985C > T, p.Arg2329*) demonstrating that not all FHS cases are caused by mutations in exon 34 of SRCAP.
  
  
  CONCLUSIONS
  Our data confirm a mutational hot spot in the final exon of SRCAP in the majority of FHS patients but also show that exon 33 of this gene can be affected.
authors.affiliation: Institut für Vegetative Anatomie, Charité - Universitätsmedizin Berlin, Berlin, Germany. wenke.seifert@charite.de.
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. meinecke@uke.uni-hamburg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Meinecke
authors.affiliation: Institut für Medizinische Genetik, Universität Rostock, Rostock, Germany. gkrueger@med.uni-rostock.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Krüger
authors.affiliation: Genetikum Stuttgart, Stuttgart, Germany. rossier@genetikum.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Rossier
authors.affiliation: Praxis für Humangenetik Cottbus, Cottbus, Germany. w.heinritz@humangenetik-cottbus.de.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Heinritz
authors.affiliation: Endokrinologikum Hamburg, Hamburg, Germany. achim.wuesthof@endokrinilogicum.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Wüsthof
authors.affiliation: Institut für Medizinische Genetik und Humangenetik, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. denise.horn@charite.de.
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D018388:Codon, Terminator; D000251:Adenosine Triphosphatases; C119652:SRCAP protein, human