Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene.

Franco Laccone (1) , Katharina Schoner (1) , Birgit Krabichler (1) , Britta Kluge (1) , Robin Schwerdtfeger (1) , Bernt Schulze (1) , Johannes Zschocke (1) , Helga Rehder (1)

1 Institute of Medical Genetics

We report on three hydropic fetuses of 17, 22 and 25 gestational weeks from three distinct families presenting with Desbuquois dysplasia type 1. All fetuses showed brachymelia and characteristic dysmorphic features. X-ray studies revealed delta-shaped extraphalangeal bones and disease-specific prominence of the lesser trochanter, varying in severity with fetal age. Early lethal manifestation of the disorder was reflected in lung hypoplasia and in early death of similarly affected siblings in cases 1 and 2. All families were German Caucasians by descent. Sequence analysis of the CANT1 gene revealed two frameshift mutations, c.228_229insC and c.277_278delCT, in homozygous and compound heterozygous configuration respectively and a homozygously novel missense mutation, c.336C>A (p.D112E) located within a higly conserved region of exon 2. Haplotype analyses by high-resolution single nucleotide polymorphism array showed that the haplotype associated with c.228_229insC may be traced to a single founder in the German population.

Mots clés: Desbuquois syndrome; CANT1 mutation; Skeletal dysplasia

Franco Laccone, Katharina Schoner, Birgit Krabichler, Britta Kluge, Robin Schwerdtfeger, et al.. Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene.. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2011.101⟩. ⟨hal-00649451⟩