Hereditary peripheral neuropathies diagnosed by next-generation sequencing

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• Next-generation sequencing (NGS) offers enhanced efficiency for sequencing multiple genes compared to traditional Sanger sequencing.
• NGS is increasingly utilized for diagnosing complex genetic disorders involving multiple genes.
• Hereditary peripheral neuropathies are a group of genetic disorders affecting the peripheral nervous system.

Purpose of the Study:

• To compare the diagnostic yield of next-generation sequencing (NGS) versus Sanger sequencing for hereditary peripheral neuropathy.
• To evaluate the effectiveness of NGS in identifying genetic causes of peripheral neuropathy.

Main Methods:

• Retrospective analysis of 103 patient samples investigated for hereditary peripheral neuropathy (2012-2014).
• Exclusion of PMP22 duplication/deletion.
• Analysis of 96 samples using NGS with physical enrichment targeting 52 hereditary peripheral neuropathy genes.

Main Results:

• A genetic cause was identified in 35% of patients with peripheral neuropathy.
• Next-generation sequencing identified 28 point mutations, accounting for 27% of diagnoses.
• A significant portion of identified mutations were in genes not previously routinely tested.

Conclusions:

• Next-generation sequencing demonstrated a higher diagnostic yield for hereditary peripheral neuropathy compared to previous methods.
• NGS enabled the identification of pathogenic point mutations in genes not typically analyzed by Sanger sequencing.
• This study highlights the value of NGS in expanding the diagnostic capabilities for hereditary peripheral neuropathies.