Improving genetic diagnosis by whole exome sequencing in rare hereditary peripheral neuropathies

Abstract

Inherited peripheral neuropathies (IPN) are rare neuromuscular diseases including the hereditary sensory neuropathies, hereditary motor neuropathies, and hereditary motor sensory neuropathies. Whole Exome Sequencing (WES) is a powerful tool in genetic diagnosis because most of the pathogenic mutations that lead to the development of diseases in this group of conditions are located in exons and splice sites and currently over 80 genes are involved with this rare group of conditions. We reported 2 patients with the clinical diagnosis of rare IPN achieving the mutation confirmation through WES. The first girl has the clinical diagnosis of hereditary sensory and autonomic neuropathy type IV with multiple complications due to complete lack of pain sensation and autonomic disturbance. A known NTRK1 mutation and a novel NTRK1 frameshift variant are identified through WES. Another boy has the clinical diagnosis of progressive peripheral motor and sensory axonal neuropathy with sensory ataxia. WES confirmed a heterozygous de novo NEFL missense mutation with negative family screening so confirming the autosomal dominant inheritance. Confirmed diagnosis for these 2 patients allows the arrangement of necessary medical care and the counseling of long term prognosis.