Hereditary Peripheral Neuropathies: NGS Testing
[A Test in Focus]
Six new next-generation sequencing (NGS) panels for the evaluation of hereditary peripheral neuropathies are now available to the Mayo Clinic practice and Mayo Medical Laboratories clients.
Hereditary peripheral neuropathies are quite varied in their presentations and even more diverse in terms of their specific genetic causes. While they can sometimes be framed in terms of the extent of weakness, sensory involvement, and/or autonomic involvements, it is difficult to discern the appropriate test for many patients.
A comprehensive testing approach with next-generation sequencing has been studied to show greater value in testing, and is therefore recommended.
The Clinical Perspective
The Laboratory Perspective
PNPAN — Peripheral Neuropathy Expanded Panel by Next Generation Sequencing
Inherited peripheral neuropathies are a relatively common diverse group of disorders with heterogeneous genetic causes
Genetic testing can help distinguish specific inherited disorders from sporadic, idiopathic, or acquired forms of neuropathy
A comprehensive diagnostic genetic test is useful to establish the genetic cause in these clinical groups
The absence of a genetic mutation in the interrogated genes does not eliminate the possibility of a hereditary peripheral neuropathy
How to Use This Test
As you consider inherited peripheral neuropathy in the differential diagnosis, the following information may be useful to determine a genetic cause and appropriate use of the test panels.
There are 5 major categories of inherited peripheral neuropathies with isolated nerve involvement: 1) hereditary motor and sensory neuropathy (HMSN), also referred as Charcot Marie Tooth (CMT); 2) hereditary sensory and autonomic neuropathy (HSAN), or hereditary sensory neuropathy (HSN), if autonomic dysfunction is absent; and 3) distal hereditary motor neuropathy (dHMN); 4) Hereditary spastic paraplegia (HSP) with neuropathy (complicated form, also referred to as HSMN type 5); 5) Syndromic or metabolic disorders with diverse organ involvements including nerve, some with available or evolving therapies.
Inherited peripheral neuropathies may also show involvement of the central nervous system, as in hereditary spastic paraplegia (HSP) with neuropathy (complicated form, also referred to as HSMN type 5) or be part of a systemic syndromic or metabolic disorder.
Given the considerable phenotypic overlap and the broad genetic heterogeneity of inherited peripheral neuropathies, a comprehensive diagnostic genetic test is useful to establish the genetic cause in these clinical groups.
This panel is useful for diagnosis of inherited peripheral neuropathies with isolated nerve involvement or associated with other organ system or associated with metabolic syndromes with known causal genes
There are regions of the genes DNMT1, HSPD1, INF2, NIPA1, NTRK1, REEP1, SBF2, and SLC16A2 that cannot be effectively amplified and sequenced as a result of technical limitations of the assay, including regions of homology, high GC-rich content, and repetitive sequences