Diagnosis; Mutation Confirmation

It is estimated that ~80% of individuals with a clinical diagnosis of HNPP will carry the deletion encompasing PMP22. The remaining 20% are predicted to carry a deleterious point mutation in the PMP22 gene

Establish or confirm diagnosis

The diagnosis of HNPP is established in an adult with recurrent focal compression neuropathies who has a family history consistent with autosomal dominant inheritance. PMP22 is the only gene known to be associated with HNPP. A contiguous gene deletion of chromosome 17p11.2 that includes PMP22 is present in approximately 80% … The diagnosis of HNPP is established in an adult with recurrent focal compression neuropathies who has a family history consistent with autosomal dominant inheritance. PMP22 is the only gene known to be associated with HNPP. A contiguous gene deletion of chromosome 17p11.2 that includes PMP22 is present in approximately 80% of affected individuals; the remaining 20% have a mutation in PMP22. View more

All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). This chemistry and analysis pipeline provides a highly sensitive and specific detection of sequence and copy number alterations in a single assay that … All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). This chemistry and analysis pipeline provides a highly sensitive and specific detection of sequence and copy number alterations in a single assay that exceeds the previous gold standard of Sanger sequence and MLPA. Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All genes have >1000x mean read depth coverage, with a minimum 200x coverage at a single nucleotide resolution. Mitochondrial DNA testing is validated for heteroplasmy detection sensitivity of 2-5%. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. View more

Mutations identified are repeated in an independent assay

Tests performed
Entire test performed in-house

Methodology predicted to detect >99% of mutations identified in the regions screened

Is proficiency testing performed for this test? Help
No

Software used to interpret novel variations Help
May include, but not restricted to SNP&Go, SIFT, Polyphen2, dbSNP, ASSEDA

Laboratory's policy on reporting novel variations Help
All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request.