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Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population.
Greenbaum, Lior; Ben-David, Merav; Nikitin, Vera; Gera, Orna; Barel, Ortal; Hersalis-Eldar, Adi; Shamash, Jana; Shimshoviz, Noam; Reznik-Wolf, Haike; Shohat, Mordechai; Dominissini, Dan; Pras, Elon; Dori, Amir.
Afiliación
  • Greenbaum L; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
  • Ben-David M; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.
  • Nikitin V; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Gera O; Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
  • Barel O; Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
  • Hersalis-Eldar A; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Shamash J; Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
  • Shimshoviz N; The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel.
  • Reznik-Wolf H; Wohl Institute of Translational Medicine, Sheba Medical Center, Tel Hashomer, Israel.
  • Shohat M; Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
  • Dominissini D; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
  • Pras E; The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel.
  • Dori A; Wohl Institute of Translational Medicine, Sheba Medical Center, Tel Hashomer, Israel.
Ann Clin Transl Neurol ; 8(6): 1260-1268, 2021 06.
Article en En | MEDLINE | ID: mdl-33973728
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Judíos / Enfermedad de Charcot-Marie-Tooth / Chaperonas Moleculares / Proteínas de Choque Térmico Tipo de estudio: Diagnostic_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Ann Clin Transl Neurol Año: 2021 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Judíos / Enfermedad de Charcot-Marie-Tooth / Chaperonas Moleculares / Proteínas de Choque Térmico Tipo de estudio: Diagnostic_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Ann Clin Transl Neurol Año: 2021 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos