Coffin-Siris syndrome: phenotypic evolution of a novel SMARCA4 mutation

Am J Med Genet A. 2014 Jul;164A(7):1808-14. doi: 10.1002/ajmg.a.36533. Epub 2014 Apr 3.

Abstract

Coffin-Siris Syndrome (CSS) is an intellectual disability disorder caused by mutation of components of the SWI/SNF chromatin-remodeling complex. We describe the evolution of the phenotypic features for a male patient with CSS from birth to age 7 years and 9 months and by review of reported CSS patients, we expand the phenotype to include neonatal and infantile hypertonia and upper airway obstruction. The propositus had a novel de novo heterozygous missense mutation in exon 17 of SMARCA4 (NM_001128849.1:c.2434C>T (NP_001122321.1:p.Leu812Phe)). This is the first reported mutation within motif Ia of the SMARCA4 SNF2 domain. In summary, SMARCA4-associated CSS is a pleiotropic disorder in which the pathognomic clinical features evolve and for which the few reported individuals do not demonstrate a clear genotype-phenotype correlation.

Keywords: choanal stenosis; chromatin remodeling; expressivity; intellectual disability; scoliosis.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Brain / pathology
  • Child
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • Face / abnormalities*
  • Facies
  • Genetic Association Studies*
  • Genetic Loci
  • Hand Deformities, Congenital / diagnosis*
  • Hand Deformities, Congenital / genetics*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Micrognathism / diagnosis*
  • Micrognathism / genetics*
  • Mutation*
  • Neck / abnormalities*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Phenotype*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*

Substances

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

Supplementary concepts

  • Coffin-Siris syndrome

Associated data

  • RefSeq/NM_001128849
  • RefSeq/NP_001122321