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) mutati...
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doaj-dd5597ef35844c088b00410a5cdcd5a62021-05-30T16:53:11ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-06-01861260126810.1002/acn3.51362Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian populationLior Greenbaum0Merav Ben‐David1Vera Nikitin2Orna Gera3Ortal Barel4Adi Hersalis‐Eldar5Jana Shamash6Noam Shimshoviz7Haike Reznik‐Wolf8Mordechai Shohat9Dan Dominissini10Elon Pras11Amir Dori12The Danek Gertner Institute of Human Genetics Sheba Medical Center Tel Hashomer IsraelDepartment of Neurology Sheba Medical Center Tel Hashomer IsraelDepartment of Neurology Sheba Medical Center Tel Hashomer IsraelSackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelThe Genomic Unit Sheba Cancer Research Center, Sheba Medical Center Tel Hashomer IsraelDepartment of Neurology Sheba Medical Center Tel Hashomer IsraelThe Danek Gertner Institute of Human Genetics Sheba Medical Center Tel Hashomer IsraelThe Genomic Unit Sheba Cancer Research Center, Sheba Medical Center Tel Hashomer IsraelThe Danek Gertner Institute of Human Genetics Sheba Medical Center Tel Hashomer IsraelSackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelSackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelThe Danek Gertner Institute of Human Genetics Sheba Medical Center Tel Hashomer IsraelSackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelAbstract 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.https://doi.org/10.1002/acn3.51362 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lior Greenbaum Merav Ben‐David Vera Nikitin Orna Gera Ortal Barel Adi Hersalis‐Eldar Jana Shamash Noam Shimshoviz Haike Reznik‐Wolf Mordechai Shohat Dan Dominissini Elon Pras Amir Dori |
spellingShingle |
Lior Greenbaum Merav Ben‐David Vera Nikitin Orna Gera Ortal Barel Adi Hersalis‐Eldar Jana Shamash Noam Shimshoviz Haike Reznik‐Wolf Mordechai Shohat Dan Dominissini Elon Pras Amir Dori Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population Annals of Clinical and Translational Neurology |
author_facet |
Lior Greenbaum Merav Ben‐David Vera Nikitin Orna Gera Ortal Barel Adi Hersalis‐Eldar Jana Shamash Noam Shimshoviz Haike Reznik‐Wolf Mordechai Shohat Dan Dominissini Elon Pras Amir Dori |
author_sort |
Lior Greenbaum |
title |
Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population |
title_short |
Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population |
title_full |
Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population |
title_fullStr |
Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population |
title_full_unstemmed |
Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population |
title_sort |
early and late manifestations of neuropathy due to hspb1 mutation in the jewish iranian population |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2021-06-01 |
description |
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. |
url |
https://doi.org/10.1002/acn3.51362 |
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