Missense variant in UBA2 associated with aplasia cutis congenita, duane anomaly, hip dysplasia and other anomalies: A possible new disorder involving the SUMOylation pathway

Am J Med Genet A. 2017 Mar;173(3):758-761. doi: 10.1002/ajmg.a.38078. Epub 2017 Jan 22.

Abstract

We report a patient with aplasia cutis congenita, Duane anomaly, hip dysplasia, and other anomalies who had a de novo missense variant in UBA2, which encodes for a protein involved in the SUMOylation pathway. It has previously been suggested that UBA2 haploinsufficiency underlies scalp defects in the 19q13.11 deletion syndrome. We propose that disturbance of the SUMOylation pathway, mediated by pathogenic variants in UBA2, is a novel mechanism for aplasia cutis congenita and other phenotypic abnormalities. © 2017 Wiley Periodicals, Inc.

Keywords: SUMOylation; aplasia cutis congenita; scalp defects.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Child, Preschool
  • Duane Retraction Syndrome / diagnosis
  • Duane Retraction Syndrome / genetics*
  • Ectodermal Dysplasia / diagnosis
  • Ectodermal Dysplasia / genetics*
  • Exome
  • Facies
  • Female
  • Genetic Association Studies
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Hip Dislocation / diagnosis
  • Hip Dislocation / genetics*
  • Humans
  • Mutation, Missense*
  • Phenotype
  • Radiography
  • Sumoylation
  • Tomography, X-Ray Computed
  • Ubiquitin-Activating Enzymes / genetics*
  • Ubiquitin-Activating Enzymes / metabolism

Substances

  • UBA2 protein, human
  • Ubiquitin-Activating Enzymes