title: Identification of novel ROR2 gene mutations in Indian children with Robinow syndrome.
abstract: OBJECTIVE
  Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients, oral manifestations are more prominent, while hemivertebrae and scoliosis rarely occur and facial abnormalities tend to be milder.
  
  
  METHODS
  Three unrelated patients from different parts of India were studied. These patients were diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had fetal facies and micropenis but unusually mild skeletal features. This patient's mother had mild affection in the form of short stature and prominent eyes. Testosterone response to human chorionic gonadotropin was investigated in two patients and were normal. The exons and exon-intron boundaries of the ROR2 gene were sequenced for all probands. Bioinformatics analysis was done for putative variants using SIFT, PolyPhen2 and Mutation Taster.
  
  
  RESULTS
  Patients 1, 2 and 3 were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3 and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be performed in an ongoing pregnancy in one family and the fetus was confirmed to be unaffected.
  
  
  CONCLUSIONS
  ROR2 mutations were documented for the first time in the Indian population. Knowledge of the molecular basis of the disorder served to provide accurate counseling and prenatal diagnosis to the families.
authors.affiliation: Genetic Research Center, NIRRH, Mumbai, India. E-ma-il: paragtmd@gmail.com.
authors.forename: Parag M
authors.initials: PM
authors.lastname: Tamhankar
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Vasudevan
authors.forename: Shweta
authors.initials: S
authors.lastname: Kondurkar
authors.forename: K
authors.initials: K
authors.lastname: Yashaswini
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Agarwalla
authors.forename: Mohandas
authors.initials: M
authors.lastname: Nair
authors.forename: T V
authors.initials: TV
authors.lastname: Ramkumar
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaubal
authors.forename: Vasundhara Sridhar
authors.initials: VS
authors.lastname: Chennuri
mesh_terms: D001848:Bone Diseases, Developmental / Q000235:genetics; D002648:Child; D003241:Consanguinity; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007194:India; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D019767:Maxillofacial Abnormalities / Q000235:genetics*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D013131:Spine / Q000002:abnormalities*
chemical_list: C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors