This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR-FAP).

Inherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients' management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation.

Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.

Twenty-four consecutive patients with familial amyloidosis with polyneuropathy (type 1), who were at different stages of the disease were investigated. The purpose was to report the electrophysiological features and to compare them with those found in other generalized neuropathies; 12 cases were familiar and 12 cases were sporadic. The diagnosis was confirmed by examining the occurrence of amyloid substance in rectal or skin biopsies or both. Single fiber EMG with fiber density determination showed signs of collateral innervation, prominent in advanced cases, and a disturbance of neuromuscular function similar to that of progressive spinal motorneuron disease. Action potentials from afferent fibers were not obtained in 91% of the nerves in the lower and 49% of the nerves in the upper extremities. When sensory or motor or slightly subnormal. The neurophysiological findings indicate a symmetrical axonal degeneration, starting in the legs. Familial amyloidosis with polyneuropathy should be suspected in cases of rapidly progressing polyneuropathy of axonal type with onset in middle age, irrespective of whether they are hereditary or not.