Identification of two novel homozygous nonsense mutations in TRAPPC9 in two unrelated consanguineous families with intellectual Disability from Iran

Mol Genet Genomic Med. 2021 Dec;9(12):e1610. doi: 10.1002/mgg3.1610. Epub 2021 Jan 29.

Abstract

Background: Pathogenic mutations in TRAPPC9 are associated with autosomal recessive Intellectual Disability (ID), a major public health issue that affects about 1-3% of children worldwide.

Method: Clinical evaluation, magnetic resonance imaging, peripheral blood karyotype, Multiplex ligation-dependent probe amplification (MLPA), array CGH, and whole-exome sequencing were used to characterize etiology in three patients from two unrelated consanguineous families of Iranian descent with intellectual disability.

Results: Whole-exome sequencing showed two novel homozygous nonsense mutations (c.937C>T) in exon 3 and (c.3103C>T) in exon 19 of TRAPPC9 (NM_031466.7) in two unrelated consanguineous families.

Conclusion: The two novel variants found in TRAPPC9 caused truncated protein and clinical manifestations such as ID, developmental delay, microcephaly, and brain abnormalities in three patients.

Keywords: TRAPPC9; Iran; intellectual disability; nonsense mutation.

MeSH terms

  • Adolescent
  • Alleles
  • Child
  • Child, Preschool
  • Codon, Nonsense*
  • Consanguinity*
  • DNA Mutational Analysis
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Homozygote*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Iran
  • Magnetic Resonance Imaging
  • Male
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA

Substances

  • Codon, Nonsense
  • Intercellular Signaling Peptides and Proteins
  • TRAPPC9 protein, human