A Family with Distal Hereditary Motor Neuropathy and a K141Q Mutation of Small Heat Shock Protein &lt;i&gt;HSPB1&lt;/i&gt;

Maeda, Kengo; Idehara, Ryo; Hashiguchi, Akihiro; Takashima, Hiroshi

doi:10.2169/internalmedicine.53.2843

Cited by 24 publications

(13 citation statements)

References 14 publications

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“…Starting in May 2012, a targeted resequencing system using the Illumina Miseq platform (Illumina, San Diego, CA, USA) was introduced for mutation screening. This system targeted a panel of 60 disease‐causing or candidate genes of IPNs, and the specific design and workflow were illustrated previously (Maeda et al, ) .…”

Section: Methodsmentioning

confidence: 99%

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Tanabe

Higuchi

Yuan

et al. 2018

J Peripheral Nervous Sys

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Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.

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Section: Methodsmentioning

confidence: 99%

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Tanabe

Higuchi

Yuan

et al. 2018

J Peripheral Nervous Sys

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“…These genes contain 40 known disease‐causing genes and 20 candidate genes of IPNs. The library preparation and sequencing were carried out following the workflow as described elsewhere . Till July 2014, we finished mutation screening by means of this sequencing platform in 460 cases.…”

Section: Methodsmentioning

confidence: 99%

Clinical and mutational spectrum of Japanese patients with Charcot‐Marie‐Tooth disease caused by GDAP1 variants

et al. 2017

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“…Age of onset is usually around 30 years, upper limbs are involved with time, and the rate of progression is slow with a minority of patients requiring a wheelchair in their seventies. So far, 25 HSPB1 mutations have been reported in more than 42 families, and five HSPB8 mutations in approximately nine families [Benndorf et al, 2014;DiVincenzo et al, 2014;Maeda et al, 2014;Ylikallio et al, 2014;Ghaoui et al, 2015;Stancanelli et al, 2015;Ylikallio et al, 2015;Capponi et al, 2016]. When considering HSPB3 (HSPL27) mutations, a unique missense mutation was reported in two dHMN siblings [Kolb et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations

et al. 2017

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In this study, we describe the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, we identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (four index patients/510; 0.8%) genes. Patients have slowly progressive distal (100%) and proximal (13%) weakness in lower limbs (100%), mild lower limbs sensory involvement (31%), foot deformities (73%), progressive distal upper limb weakness (29%), mildly raised serum creatine kinase levels (100%), and central nervous system involvement (9%). We identified 12 HSPB1 and four HSPB8 mutations, including five and three not previously reported. Transmission was either dominant (78%), recessive (3%), or de novo (19%). Three missense mutations in HSPB1 (Pro7Ser, Gly53Asp, and Gln128Arg) cause hyperphosphorylation of neurofilaments, whereas the C-terminal mutant Ser187Leu triggers protein aggregation. Two frameshift mutations (Leu58fs and Ala61fs) create a premature stop codon leading to proteasomal degradation. Two mutations in HSPB8 (Lys141Met/Asn) exhibited increased binding to Bag3. We demonstrate that HSPB1 and HSPB8 mutations are a major cause of inherited motor axonal neuropathy. Mutations lead to diverse functional outcomes further demonstrating the pleotropic character of small heat shock proteins.

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A Family with Distal Hereditary Motor Neuropathy and a K141Q Mutation of Small Heat Shock Protein <i>HSPB1</i>

Cited by 24 publications

References 14 publications

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Clinical and mutational spectrum of Japanese patients with Charcot‐Marie‐Tooth disease caused by GDAP1 variants

Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations

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