A hereditary spastic paraplegia predominant phenotype caused by variants in the NEFL gene.

Introduction: This study reports a large series of patients with a clinical picture dominated by spastic paraplegia in whom variants in the NEFL gene, a known cause for Charcot-Marie-Tooth disease, were identified.

Methods: Index patients referred for a suspicion of hereditary spastic paraplegia (HSP) were clinically assessed and genetic analysis by next-generation sequencing was undertaken. Additional family members were clinically examined and subjected to targeted testing.

Pulmonary Fibrosis and a TERT Founder Mutation With a Latency Period of 300 Years.

Background: Germline mutations in the gene encoding TERT cause haploinsufficiency with subsequent telomere shortening. TERT mutations are associated with short telomere syndromes, such as pulmonary fibrosis (PF), which is often the first manifestation of a short telomere syndrome. Telomere length is heritable, and progeny of telomerase mutation carriers are known to have shorter telomeres.

Clinical and genetic characterization of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy caused by a plakophilin-2 splice mutation.

Objectives: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index patients, a genetic predisposition is demonstrated. The purpose of this study was to examine a plakophilin-2 (PKP2) splice site mutation, c.