Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population

Abstract

Objective: Mutations in the HSPB1 gene are associated with a distal hereditary motor neuropathy type 2 (dHMN2) or Charcot-Marie-Tooth disease type 2F (CMT2F), usually with autosomal dominant inheritance. This study aimed to describe the phenotype of the HSPB1 c.407G>T (p.Arg136Leu) mutation at early and late stages of the disease course. Methods: We identified this mutation (previously reported in patients from Italy) in a heterozygous state, among 14 individuals from eight families of Jewish Iranian descent. The clinical, electrophysiological and ultrasonographic features were evaluated during early (less than 5 years, N = 9) or late disease course (N = 5). Results: The majority of subjects were males with a mean age at onset of 43.4 years (range 21-67). Common initial symptoms were gait imbalance, distal (often asymmetric) lower limb weakness and feet numbness. Neurological examination in early disease course showed distal lower extremity weakness in nearly all cases, and absent Achilles tendon reflex in about half. A minority had distal loss of pain, vibration or position sensation. These findings were more prevalent in late disease stage. Electrodiagnostic studies demonstrated a length-dependent axonal motor neuropathy, with typical preferential involvement of the tibial nerve. Muscle ultrasound showed a corresponding length-dependent increase of homogeneous echo-intensity, most noticeably in the gastrocnemius. One patient had a dual diagnosis of CMT2F and CMT2W. Interpretation: The HSPB1 c.407G>G (p.Arg136Leu) mutation causes an adult-onset, predominantly motor, axonal neuropathy in individuals of Jewish Iranian descent. Variable manifestations are noticed, and sensory involvement is more prominent in prolonged disease duration.

A Young Man With Hereditary Motor And Sensory Neuropathy: A Rare Genetic Association

“…10 In recent years, a few familial and sporadic HMSN cases caused by rare site mutations have been reported due to the widespread use of gene sequencing technology. 11 This case study features a young man who initially had subtle lower limb weakness that progressively worsened. Over the course of seven months, he gradually noticed wasting in both lower limbs, beginning in the distal region.…”

Hereditary motor and sensory neuropathy with SOD1-mutant: A case report

“…[8] With the widespread application of gene sequencing technology, some familial and sporadic HMSN cases caused by rare site mutations have been reported in recent years. [9] Studies have shown that HMSN is often accompanied by acute, subacute or chronic inflammatory responses, which can lead to an increase in oxidative stress and reactive oxygen species. Therefore, oxidative stress and neuroinflammation may be involved in the pathogenesis of HMSN.…”

“…[ 8 ] With the widespread application of gene sequencing technology, some familial and sporadic HMSN cases caused by rare site mutations have been reported in recent years. [ 9 ]…”

Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation in HSPB1 Gene: A Case Series

“…In the following years, studies and reports supplemented this conclusion [ 5 ]. The clinical phenotypes caused by HSPB1 gene mutation have certain heterogeneity in symptoms and onset age [ 6 ]. Even in the same family, clinical manifestations varied from muscle cramps as the only presenting symptom to a classic distal motor-sensory axonal neuropathy [ 7 ].…”