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Position effects of 22q13 rearrangements on candidate genes in Phelan-McDermid syndrome.

Sujata SrikanthLavanya JainCinthya Zepeda-MendozaLauren CascioKelly JonesRini PaulyBarb DuPontCurtis RogersSara SarasuaKaty PhelanCynthia MortonLuigi Boccuto
Published in: PloS one (2021)
Phelan-McDermid syndrome (PMS) is a multi-system disorder characterized by significant variability in clinical presentation. The genetic etiology is also variable with differing sizes of deletions in the chromosome 22q13 region and types of genetic abnormalities (e.g., terminal or interstitial deletions, translocations, ring chromosomes, or SHANK3 variants). Position effects have been shown to affect gene expression and function and play a role in the clinical presentation of various genetic conditions. This study employed a topologically associating domain (TAD) analysis approach to investigate position effects of chromosomal rearrangements on selected candidate genes mapped to 22q13 in 81 individuals with PMS. Data collected were correlated with clinical information from these individuals and with expression and metabolic profiles of lymphoblastoid cells from selected cases. The data confirmed TAD predictions for genes encompassed in the deletions and the clinical and molecular data indicated clear differences among individuals with different 22q13 deletion sizes. The results of the study indicate a positive correlation between deletion size and phenotype severity in PMS and provide evidence of the contribution of other genes to the clinical variability in this developmental disorder by reduced gene expression and altered metabolomics.
Keyphrases
  • gene expression
  • genome wide
  • copy number
  • dna methylation
  • electronic health record
  • big data
  • mass spectrometry
  • healthcare
  • case report
  • binding protein
  • social media
  • health information
  • genome wide identification