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

• DOI: 10.1186/s12881-014-0127-0
• Publication Date: 2014-12-01T11:53:16Z
• Authors: Wenke Seifert; Peter Meinecke; Gabriele Krüger; Eva Rossier; Wolfram Heinritz; Achim Wüsthof; Denise Horn
• Keywords: Human genetics; Sanger sequencing; Haploinsufficiency

Floating-Harbor syndrome is a rare autosomal dominant short stature with retarded speech development, intellectual disability and dysmorphic facial features. Recently mutations almost exclusively located in exon 34 of the Snf2-related CREBBP activator protein gene were identified to cause FHS. Here we report genetic analysis 5 patients fulfilling diagnostic criteria FHS obtained by Sanger sequencing. All them presented stature, delay as well psychomotor typical dysmorphism. Three showed good response growth hormone treatment. Two demonstrate novel, heterozygous de novo frameshift (c.7396delA c.7218dupT) leading premature stop SRCAP (p.Val2466Tyrfs*9 p.Gln2407Serfs*36, respectively). In two further found already known 34, c.7330C > T c.7303C T, respectively, which also lead codons: p.Arg2444* p.Arg2435*. one patient, novel mutation 33 (c.6985C p.Arg2329*) demonstrating that not all cases are caused SRCAP. Our data confirm mutational hot spot final majority but show this can be affected.