17p12

17p12 is a cytogenetic band on the short arm of chromosome 17. The region is best known for containing the PMP22 gene, whose dosage is a major determinant of disease within this locus, though other genes reside there as well. 17p12 is a well-characterized site for recurrent copy-number variation because flanking segmental duplications promote non-allelic homologous recombination, leading to deletions or duplications.

Copy-number changes in 17p12 are associated with Charcot-Marie-Tooth disease type 1A (CMT1A) from PMP22 duplication and hereditary neuropathy with liability to pressure palsies (HNPP) from PMP22 deletion. Duplications are typically about 1.5 megabases and extend from 17p11.2 to p12; deletions span the same region. The resulting phenotypes include demyelinating distal neuropathies with weakness and sensory loss; HNPP especially presents with recurrent focal weakness after minor nerve compression or trauma. Inheritance is autosomal dominant for both conditions, with variable expressivity and penetrance; de novo events occur but are less common.

Diagnosis relies on genetic testing to assess PMP22 dosage, using methods such as multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (array CGH), or targeted sequencing with copy-number analysis. Genetic counseling emphasizes the reciprocal nature of the duplication and deletion events and their associated clinical phenotypes.