De novo SETD5 loss-of-function variant as a cause for intellectual disability in a 10-year old boy with an aberrant blind ending bronchus

Am J Med Genet A. 2017 Dec;173(12):3165-3171. doi: 10.1002/ajmg.a.38461. Epub 2017 Sep 14.


Although rare, 3p microdeletion cases have been well described in the clinical literature. The clinical phenotype includes; intellectual disability (ID), growth retardation, facial dysmorphism, and cardiac malformations. Advances in chromosome microarray (CMA) testing narrowed the 3p25 critical region to a 124 kb region, and recent Whole Exome Sequencing (WES) studies have suggested that the SETD5 gene contributes significantly to the 3p25 phenotype. Loss-of-Function (LoF) variants in SETD5 are now considered a likely cause of ID. We report here a patient with a frameshift LoF variant in exon 12 of SETD5. This patient has features overlapping with other patients described with LoF SETD5 variants to include; similar facial morphology, feeding difficulties, ID, behavioral abnormalities and leg length discrepancy. In addition, he presents with an aberrant blind ending bronchus. This report adds to publications describing intragenic mutations in SETD5 and supports the assertion that de novo LoF mutations in SETD5 present with an overlapping but distinct phenotype in comparison with 3p25 microdeletion syndromes.

Keywords: 3p microdeletion; 3p25, SETD5; aberrant blind ending bronchus; intellectual disability; loss of function.

Publication types

  • Case Reports

MeSH terms

  • Bronchi / abnormalities*
  • Child
  • Chromosome Deletion
  • Chromosomes, Human, Pair 3 / genetics
  • Cohort Studies
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics*
  • Exons / genetics
  • Frameshift Mutation
  • Heterozygote
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Loss of Function Mutation*
  • Male
  • Methyltransferases / genetics*
  • Phenotype


  • Methyltransferases
  • SETD5 protein, human

Supplementary concepts

  • Chromosome 3, monosomy 3p25