PMP22 gene diagnostic testing in Southwest Finland in 2005-2020. An observational, register-based study.

Pathogenic variants of PMP22 cause Charcot-Marie-Tooth disease type 1 A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). As CMT1A is the most common inherited neuropathy and the most common pathogenic PMP22 variants are duplications and deletions, focused analysis of this gene remains relevant in the era of large gene panels and exome studies. We investigated the use and findings of PMP22 gene analyses carried out at Turku University Hospital (TUH; Turku, Finland) in 2005-2020. Using the electronic medical record system at TUH, we identified all patients who underwent PMP22 genetic diagnostic testing in 2005-2020. Data on testing indication, clinical features, relevant family history, genetic testing results, and final neurological diagnoses were collected. Out of total 244 tests, 64 (26%) provided a diagnostic finding. The diagnostic yield was 33% for PMP22 deletions that were the most common variants (58%), and 23% for PMP22 duplications. Highest yield (45%) was in patients with both clinical presentation and family history suggestive of a genetic neuropathy. The yearly diagnostic incidence of PMP22 related neuropathies during the study period was 0.89/100 000; 0.6/100 000 for PMP22 deletions and 0.4/100 000 for PMP22 duplications. In clinical diagnostic use of the PMP22 gene analyses, the majority of diagnostic findings were related to HNPP rather than CMT1A. We suggest that HNPP merits more research attention.