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Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome

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...

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Autores principales: Seifert, Wenke, Meinecke, Peter, Krüger, Gabriele, Rossier, Eva, Heinritz, Wolfram, Wüsthof, Achim, Horn, Denise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412025/
https://www.ncbi.nlm.nih.gov/pubmed/25433523
http://dx.doi.org/10.1186/s12881-014-0127-0
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author Seifert, Wenke
Meinecke, Peter
Krüger, Gabriele
Rossier, Eva
Heinritz, Wolfram
Wüsthof, Achim
Horn, Denise
author_facet Seifert, Wenke
Meinecke, Peter
Krüger, Gabriele
Rossier, Eva
Heinritz, Wolfram
Wüsthof, Achim
Horn, Denise
author_sort Seifert, Wenke
collection PubMed
description 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.
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spelling pubmed-44120252015-04-29 Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome Seifert, Wenke Meinecke, Peter Krüger, Gabriele Rossier, Eva Heinritz, Wolfram Wüsthof, Achim Horn, Denise BMC Med Genet Research Article 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. BioMed Central 2014-11-30 /pmc/articles/PMC4412025/ /pubmed/25433523 http://dx.doi.org/10.1186/s12881-014-0127-0 Text en © Seifert et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Seifert, Wenke
Meinecke, Peter
Krüger, Gabriele
Rossier, Eva
Heinritz, Wolfram
Wüsthof, Achim
Horn, Denise
Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title_full Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title_fullStr Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title_full_unstemmed Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title_short Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome
title_sort expanded spectrum of exon 33 and 34 mutations in srcap and follow-up in patients with floating-harbor syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412025/
https://www.ncbi.nlm.nih.gov/pubmed/25433523
http://dx.doi.org/10.1186/s12881-014-0127-0
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