Identification of a novel causative mutation in the ROR2 gene in a Lebanese family with a mild form of recessive Robinow syndrome

Eur J Med Genet. 2012 Feb;55(2):103-8. doi: 10.1016/j.ejmg.2011.11.003. Epub 2011 Nov 27.

Abstract

Autosomal recessive Robinow syndrome (OMIM 268310) is a condition caused by mutations in the ROR2 gene, the receptor tyrosine kinase-like orphan receptor 2. The main characteristic features are: a face resembling that of a fetus, cleft lip and palate, mesomelic limb shortening, a micropenis in males, hydronephrosis or urinary tract infections, and skeletal and vertebral anomalies. This study reports two sisters from a consanguineous Lebanese family with an autosomal recessive Robinow syndrome. Both presented with short stature, dysmorphic facial features, and mild bone abnormalities. One of the affected girls had a malformation of her right hand: a mesoaxial polydactyly combined with a syndactyly of the 3rd and 4th fingers, and a short right 3rd metacarpal bone. Molecular analysis of the ROR2 gene revealed the presence of a previously undescribed missense mutation: p.R272C (c.814C>T), in the cysteine-rich domain of the protein. These patients are compared with other cases, and a phenotype-genotype correlation is discussed.

MeSH terms

  • Child, Preschool
  • Craniofacial Abnormalities / genetics
  • DNA Mutational Analysis
  • Female
  • Humans
  • Infant
  • Lebanon
  • Limb Deformities, Congenital / genetics*
  • Male
  • Maxillofacial Abnormalities / genetics*
  • Mutation*
  • Pedigree
  • Receptor Tyrosine Kinase-like Orphan Receptors / genetics*
  • Spine / abnormalities

Substances

  • ROR2 protein, human
  • Receptor Tyrosine Kinase-like Orphan Receptors

Supplementary concepts

  • Robinow syndrome, autosomal recessive