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