Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome

Eur J Hum Genet. 2018 Mar;26(3):293-302. doi: 10.1038/s41431-017-0042-x. Epub 2018 Jan 22.


Chromosome 22q13.3 deletion (Phelan McDermid) syndrome (PMS) is a rare genetic neurodevelopmental disorder resulting from deletions or other genetic variants on distal 22q. Pathological variants of the SHANK3 gene have been identified, but terminal chromosomal deletions including SHANK3 are most common. Terminal deletions disrupt up to 108 protein-coding genes. The impact of these losses is highly variable and includes both significantly impairing neurodevelopmental and somatic manifestations. The current review combines two metrics, prevalence of gene loss and predicted loss pathogenicity, to identify likely contributors to phenotypic expression. These genes are grouped according to function as follows: molecular signaling at glutamate synapses, phenotypes involving neuropsychiatric disorders, involvement in multicellular organization, cerebellar development and functioning, and mitochondrial. The likely most impactful genes are reviewed to provide information for future clinical and translational investigations.

Publication types

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

MeSH terms

  • Chromosome Deletion
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / pathology
  • Chromosomes, Human, Pair 22 / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Open Reading Frames*


  • Nerve Tissue Proteins
  • SHANK3 protein, human

Supplementary concepts

  • Telomeric 22q13 Monosomy Syndrome