Retinal dystrophy in an individual carrying a de novo missense variant of SMARCA4

Mol Genet Genomic Med. 2019 Jun;7(6):e682. doi: 10.1002/mgg3.682. Epub 2019 Apr 11.

Abstract

Background: Coffin-Siris syndrome (CSS) is characterized by intellectual disability, dysmorphic facial features, growth deficiency, microcephaly, and abnormalities of the fifth fingers/toes. CSS is caused by mutations in several genes of the BRG1-associated factor pathway including SMARCA4.

Methods: Whole-exome sequencing was performed on a 14-year-old female individual who presented with mild intellectual disability and dysmorphic features, tooth abnormalities, and short stature. She had brachydactyly but no aplasia or hypoplasia of the distal phalanx or nail of the fifth digit. She was also found to have retinal dystrophy that has not been previously reported in CSS.

Results: The individual presented herein was found to harbor a previously unreported de novo variant in SMARCA4.

Conclusion: This case expands the phenotypic spectrum of CSS manifestations.

Keywords: SMARCA4; Coffin-Siris syndrome; retinitis pigmentosa.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • DNA Helicases / genetics*
  • Face / abnormalities*
  • Face / pathology
  • Female
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / pathology
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Micrognathism / genetics*
  • Micrognathism / pathology
  • Mutation, Missense
  • Neck / abnormalities*
  • Neck / pathology
  • Nuclear Proteins / genetics*
  • Phenotype
  • Retina / pathology*
  • Transcription Factors / genetics*

Substances

  • Nuclear Proteins
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases

Supplementary concepts

  • Coffin-Siris syndrome