Background: Heat shock protein beta-1 (HSPB1) is a ubiquitously expressed molecular chaperone that is important in protecting cells against cellular injury. Mutations in this protein are known to cause autosomal dominant hereditary distal axonal neuropathies, including Charcot Marie Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). However, patients with HSPB1 mutations have also been described with upper motor neuron signs. We present five patients with mutations in HSPB1 who presented with a range of clinical phenotypes related to different patterns of motor neuron dysfunction. Three of these mutations have not been previously reported.
Methods: Patients were seen at our neuromuscular or amyotrophic lateral sclerosis (ALS) clinics. Gene sequencing was carried out as part of diagnostic investigations. Detailed clinical and electrophysiologic data was collected.
Results: Five patients had variants of HSPB1. Three patients had a hereditary length-dependent sensori-motor axonal neuropathy consistent with Charcot Marie Tooth type 2 (CMT2); two of these patients carried novel mutations in the C-terminal region (p.Glu186* and p.Pro170Thr). One patient had the clinical picture of ALS and a novel missense mutation (p.Arg27Leu) in the N-terminal region. Another patient had the phenotype of hereditary spastic paraparesis (HSP) associated with a missense mutation (p.Gly84Arg) already described in families with CMT or dHMN.
Conclusion: This study describes three novel mutations of HSPB1 and describes two patients with upper motor neurone signs associated with HSPB1 mutations.
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