ClinGen Dosage Sensitivity Curation Page

17p11.2 recurrent (SMS/PLS) region (includes RAI1)

  • Curation Status: Complete
  • id: ISCA-37418
  • Date last evaluated: 2013-11-21
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 3


Location Information

Select assembly: (NC_000017.10) ()

Haploinsufficiency phenotype comments:

Deletions of this region are a recurrent cause of Smith-Magenis syndrome (SMS) and are mediated by segmental duplications. Mutations in the RAI1 gene have been identified in patients with Smith-Magenis syndrome and haploinsufficiency of this gene is believed to be responsible for the majority of this phenotype. While there is some variability in the size of deletions associated with SMS, due to multiple segmental duplications in the region, all deletions contain the RAI1 gene. See GeneReview.

Evidence for triplosensitivity phenotype
PubMed ID Description
17357070 Potocki et al, (2007) report 22 patients with a 17p11.2 duplication (reciprocal to the SMS deletion) who have similar clinical findings. They also report 13 patients with duplications of variable size. They named this condition Potocki-Lupski syndrome.
20188345 Zhang et al. (2010) report 35 new patients with 17p11.2 duplications. The smallest region of overlap between 74 cases included the RAI1 gene.

Triplosensitivity phenotype comment:

Duplications of this region cause Potocki-Lupski syndrome and are mediated by segmental duplications.