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Phenotype and natural history of inherited neuropathies caused by HSJ1 c.352+1G>A mutation
  1. M Frasquet1,2,3,
  2. M J Chumillas1,3,4,
  3. J J Vílchez1,2,3,5,
  4. C Márquez-Infante6,
  5. F Palau3,7,8,9,
  6. J F Vázquez-Costa1,2,3,
  7. V Lupo3,7,
  8. C Espinós3,7,
  9. T Sevilla1,2,3,5
  1. 1 Neuromuscular Research Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
  2. 2 Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
  3. 3 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
  4. 4 Department of Clinical Neurophysiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
  5. 5 Department of Medicine, University of Valencia, Valencia, Spain
  6. 6 Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain
  7. 7 Program in Rare and Genetic Diseases and IBV/CSIC Associated Unit, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
  8. 8 Department of Genetic and Molecular Medicine, Instituto Pediátrico de Enfermedades Raras (IPER), and Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain
  9. 9 Department of Pediatrics, University of Barcelona, Barcelona, Spain
  1. Correspondence to Dr Teresa Sevilla, Department of Neurology, Hospital Universitari i Politècnic La Fe, Avenida Fernando Abril Martorell 106, Valencia 46026, Spain; sevilla_ter{at}gva.es

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Introduction

Mutations in the HSJ1 (Heat-Shock Protein J1) gene, also called DNAJB2 (DnaJ (Hsp40) homologue, subfamily B, member 2), have been recently described as a cause of hereditary neuropathies. The HSJ1 c.352+1G>A mutation in homozygote state has been reported as the causative mutation in a single family with autosomal recessive distal hereditary motor neuropathy (dHMN).1 Since then, two other families with different HSJ1 mutations have been described: one with a dHMN phenotype and the other with a Charcot-Marie-Tooth disease type 2 (CMT2) phenotype.2

We identified the HSJ1 c.352+1G>A mutation in 10 patients who underwent long-lasting follow-up. We describe their phenotype and clinical evolution.

Patients and methods

Ten patients from five different Spanish families had been diagnosed with dHMN or CMT2 at two tertiary referral centres in Spain between 1976 and 2014. They all underwent neurological examination and electrophysiological studies using standard techniques.3 Regular follow-up was performed in all cases and repeated electrophysiological studies were carried out in some patients.

All the families carried the HSJ1 c.352+1G>A homozygote pathogenic sequence variation. Family 1 was diagnosed by exome sequencing. Families 2 and 4 were diagnosed using a gene panel for genetic testing of CMT and dHMN. Families 3 and 5 were identified by mutational screening of the HSJ1 c.352+1G>A change, carried out in 52 patients from our registry, with autosomal recessive dHMN or CMT2, who still had no molecular diagnosis. In all cases, mutation was confirmed by Sanger sequencing and a segregation analysis was performed whenever possible.

All the patients and relatives included in the present study signed informed consent. The research protocols were approved by the respective institutional boards of the Ethics Committee …

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