Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome

J Clin Lab Anal. 2020 Feb;34(2):e23074. doi: 10.1002/jcla.23074. Epub 2019 Oct 16.


Background: Autosomal recessive Robinow syndrome (ARRS) is a rare genetic disorder, which affects the development of multiple systems, particularly the bones.

Objectives: The aim of this study was to investigate the genetic cause of a ARRS fetus and to evaluate the reliability of whole-exome sequencing (WES) in prenatal diagnosis on cases with indistinguishable multiple malformation.

Methods: Clinical and ultrasonic evaluations were conducted on the fetus, and multiplatform genetic techniques were used to identify the variation responsible for RS. The pathogenicity of the novel variation was evaluated by in silico methods. Western blotting (WB) and immunohistochemistry (IHC) were performed on fetal tissues after the fetus' stillbirth and postabortal autopsy.

Results: A compound heterozygous variation consisting c.613C > T and c.904C > T in ROR2 gene was identified. In silico prediction suggested that c.904C > T was a deleterious variant. IHC result demonstrated that ror2 expression level of the proband in osteochondral tissue significantly increased comparing with that of the control sample.

Conclusions: For the first time in Chinese population, we characterized a novel variation in ROR2 gene causing ARRS. This study extended the mutation spectrum of ARRS and provided a promising strategy for prenatal diagnosis of cases with ambiguous multiple deformities.

Keywords: ROR2 gene; Robinow Syndrome; immunohistochemistry; western blotting; whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amniocentesis
  • Exome Sequencing
  • Female
  • Fetus
  • Heterozygote
  • Humans
  • Limb Deformities, Congenital / diagnosis
  • Limb Deformities, Congenital / diagnostic imaging
  • Limb Deformities, Congenital / genetics*
  • Male
  • Maxillofacial Abnormalities / diagnosis
  • Maxillofacial Abnormalities / diagnostic imaging
  • Maxillofacial Abnormalities / genetics*
  • Mutation*
  • Pedigree
  • Pregnancy
  • Receptor Tyrosine Kinase-like Orphan Receptors / genetics*
  • Receptor Tyrosine Kinase-like Orphan Receptors / metabolism
  • Spine / abnormalities*
  • Spine / diagnostic imaging
  • Ultrasonography, Prenatal


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

Supplementary concepts

  • Robinow syndrome, autosomal recessive