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A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT)
  1. Elisa Giorgio1,
  2. Giovanna Vaula2,
  3. Paolo Benna3,4,
  4. Nicola Lo Buono5,11,
  5. Chiara Maria Eandi6,
  6. Daniele Dino7,
  7. Cecilia Mancini1,
  8. Simona Cavalieri8,
  9. Eleonora Di Gregorio8,
  10. Elisa Pozzi1,
  11. Marta Ferrero1,
  12. Maria Teresa Giordana2,3,
  13. Christel Depienne9,10,
  14. Alfredo Brusco1,8
  1. 1 Department of Medical Sciences, Medical Genetics Unit, University of Torino, Torino, Italy
  2. 2 Department of Neurology, Città della Salute e della Scienza University Hospital, Torino, Italy
  3. 3 Department of Neurosciences ‘Rita Levi Montalcini’, University of Torino, Torino, Italy
  4. 4 Department of Neurosciences and Mental Health, Città della Salute e della Scienza University Hospital, Torino, Piemonte, Italy
  5. 5 Department of Medical Sciences, Laboratory of Immunogenetics, University of Torino, Torino, Italy
  6. 6 Department of Surgical Sciences, Eye Clinic, University of Torino, Torino, Italy
  7. 7 Department of Neurosciences, Città della Salute e della Scienza University Hospital, Neuroradiology Unit, Torino, Italy
  8. 8 Medical Genetics, Città della Salute e della Scienza University Hospital, Torino, Italy
  9. 9 Département de Médecine translationnelle et Neurogénétique, IGBMC, CNRS UMR 7104/INSERMU964/Université de Strasbourg, Illkirch, France
  10. 10 Laboratoire de cytogénétique, Institut de génétique médicale d’Alsace, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  11. 11 San Raffaele Diabetes Research Institute (DRI), San Raffaele Hospital, Milano, Italy
  1. Correspondence to Professor Alfredo Brusco, Department of Medical Sciences, University of Torino, via Santena 19, 10126, Torino, Italy; alfredo.brusco{at}

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ClC-2 is a plasma membrane chloride channel with widespread expression in the human body, including the brain. Its function is still being studied, although it is thought to have a role in ion and water homoeostasis in the brain. ClC-2 is part of a complex containing GlialCAM and MLC1. Both these genes are associated with autosomal recessive human leukodystrophies with intramyelinic oedema. Biallelic mutations in CLCN2, encoding the ClC-2 channel, have been reported in patients with a rare form of leukoencephalopathy with ataxia (LKPAT; MIM #615651). No peculiar neurological features have been reported for this disease, although slight visual impairment due to chorioretinopathy or optic atrophy, mild ataxia, learning disabilities, and headaches are recurrent symptoms in patients. However, MRI shows a typical diagnostic pattern that consists of white matter signal abnormalities in the posterior limbs of the internal capsules, cerebral peduncles, pontine pyramidal tracts and in the middle cerebellar peduncles, associated with lower apparent diffusion coefficient values in most cases. Specific anomalies of brainstem auditory evoked potentials (BAEP) have also been described.1–3

Here, we report on a 52-year-old Moroccan woman presenting with mild and asymptomatic bilateral optic atrophy detected at a routine ophthalmological examination for presbyopia. Best-corrected high-contrast visual acuity was 20/20 in both eyes. Anterior segment and intraocular pressures were normal, and pupillary reflexes were present. On fundus biomicroscopy, mild pallor and excavation of the optic …

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  • Contributors EG designed the experimental plan, performed experiments, analysed data, and drafted and revised the paper. GV, PB, DD, CME and MTG contributed to the clinical definition to the clinical, neuroradiological and ophthalmological definition of the patient phenotype. NLB, CD, CM, SC, EDG, EP, MF and AB contributed to the experimental work and/or performed data analysis and interpretation. All authors revised the paper.

  • Funding This work was supported by MURST60% and Associazione ‘EE Rulfo per la Genetica Medica’ (to AB).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Internal Review Board Committee of the Department of Medical Sciences (University of Torino).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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