Expanded spectrum of exon 33 and 34 mutations in 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 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 frameshift mutations in exon 34 (c.7396delA and c.7218dupT) leading to premature stop mutations in (p.Val2466Tyrfs*9 and p.Gln2407Serfs*36, respectively). In two further patients we found already known 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 stop mutation in exon 33 (c.6985C>T, p.Arg2329*) demonstrating that not all FHS cases are caused by mutations in exon 34 of . Conclusions: Our data confirm a mutational hot spot in the final exon of in the majority of FHS patients but also show that exon 33 of this gene can be affected.