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Heterozygous Recurrent Mutations Inducing Dysfunction of ROR2 Gene in Patients With Short Stature

Baoheng Gui1,2,3, Chenxi Yu4,5, Xiaoxin Li6

  • 1Center for Medical Genetics and Genomics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.

Frontiers in Cell and Developmental Biology
|May 3, 2021
PubMed
Abstract

Insights

ROR2 mutations were identified in children with short stature. A specific mutation (c.1675G > A) disrupts ROR2 protein localization and affects downstream Wnt5a-ROR2 pathway signaling.

Area of Science:

  • Genetics and Molecular Biology
  • Developmental Biology
  • Endocrinology

Background:

  • ROR2 is crucial for skeletal development, acting as a receptor for Wnt5a.
  • Understanding ROR2's role is key to diagnosing and treating skeletal growth disorders.

Purpose of the Study:

  • To investigate the spectrum of ROR2 mutations in children with short stature.
  • To elucidate the molecular mechanisms underlying these mutations.

Main Methods:

  • Retrospective analysis of clinical data and whole-exome sequencing (WES) in 426 short stature patients.
  • In vitro functional assays to assess ROR2 protein expression, localization, and downstream Wnt5a-ROR2 pathway activity.

Main Results:

  • Identified 12 mutations in ROR2 (10 missense, 1 nonsense, 1 frameshift) in 21 patients.
  • The c.1675G > A mutation significantly altered ROR2 protein expression and subcellular localization.
  • This mutation also led to decreased expression of c-Jun, a downstream Wnt5a-ROR2 pathway molecule.

Conclusions:

  • Expanded the known mutational spectrum of ROR2 in short stature.
  • The c.1675G > A mutation may impair Wnt5a-ROR2 pathway signaling by affecting ROR2 protein localization and expression.
Keywords:
ROR2 genedysfunctionrecurrent mutationsshort statureskeletal development

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