SETD5 loss-of-function mutation as a likely cause of a familial syndromic intellectual disability with variable phenotypic expression

Am J Med Genet A. 2016 Sep;170(9):2322-7. doi: 10.1002/ajmg.a.37832. Epub 2016 Jul 4.

Abstract

Loss-of-function de novo mutations in the SETD5 gene, encoding a putative methyltransferase, are an important cause of moderate/severe intellectual disability as evidenced by the results of sequencing large patient cohorts. We present the first familial case of a SETD5 mutation contributing to a phenotype of congenital heart defects and dysmorphic features, with variable expression, in two siblings and their father. Interestingly, the father demonstrated only mild intellectual impairment. Family based exome sequencing combined to careful parental phenotyping may reveal a more complex clinical picture in newly recognized syndromes. © 2016 Wiley Periodicals, Inc.

Keywords: 3p deletions; SETD5; exome sequencing; intellectual disability.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Child, Preschool
  • Exome
  • Facies
  • Genetic Association Studies*
  • Genome-Wide Association Study
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inheritance Patterns
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Methyltransferases / genetics*
  • Mutation*
  • Phenotype*
  • Siblings
  • Syndrome

Substances

  • Methyltransferases
  • SETD5 protein, human