ClinGen Dosage Sensitivity Curation Page

17p12 recurrent (HNPP/CMT1A) region (includes PMP22)

  • Curation Status: Complete
  • id: ISCA-37436
  • Date last evaluated: 2016-10-13
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 3


Location Information

Select assembly: (NC_000017.10) ()
Evidence for haploinsufficiency phenotype
PubMed ID Description
20301566 GeneReviews on HNPP

Haploinsufficiency phenotype comments:

This region is the recurrent 17p12 (PMP22) deletion region, mediated by non-allelic homologous recombination between flanking paralogous low-copy repeat regions, distal and proximal CMT1A-REP. Deletion of this region is associated with autosomal dominant hereditary neuropathy with liability to pressure palsies (HNPP). HNPP is characterized by repeated focal pressure neuropathies beginning in adolescence or young adulthood. The penetrance of recurrent 17p12 (PMP22) deletion is unknown, as many individuals that carry a deletion of this region have few (or no) symptoms and are thought to remain undiagnosed. Approximately 80% of HNPP deletions are inherited. Loss-of-function mutations in the gene PMP22 (nonsense, missense, splice site, and small deletions) are also causative for HNPP.

Evidence for triplosensitivity phenotype
PubMed ID Description
20301384 GeneReviews on CMT1, includes CMT1A caused by 17p12 (PMP22) region duplication

Triplosensitivity phenotype comment:

This region is the recurrent 17p12 (PMP22) duplication region, mediated by non-allelic homologous recombination between flanking paralogous low-copy repeat regions, distal and proximal CMT1A-REP. Duplication of this region is associated with Charcot-Marie-Tooth type 1A (CMT1A). CMT1A is a neuropathy that is characterized by slowly progressive weakness and atrophy of distal muscles (hands and the legs below the knees), hearing loss, pes cavus foot deformity, hip dysplasia, and additional clinical findings. The penetrance of this duplication is thought to be near 100%; however, age of onset and severity of the condition are variable, and some carriers are not clinically recognized. Approximately 67-80% of recurrent 17p12 (PMP22) region duplications are inherited.