title: WFS1 in Optic Neuropathies: Mutation Findings in Nonsyndromic Optic Atrophy and Assessment of Clinical Severity.
abstract: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment.
  
  
  
  Retrospective molecular genetic and clinical study.
  
  
  
  Patients with OA followed at a national referral center specialized in genetic sensory diseases.
  
  
  
  Mutation screening in WFS1 was performed by Sanger sequencing. WFS1-positive patients were evaluated on visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness using time-domain (TD) or spectral-domain (SD) optical coherence tomography (OCT). Statistical analysis was performed.
  
  
  
  Mutation identification, VA values, and RNFL thickness in sectors.
  
  
  
  Biallelic WFS1 mutations were found in 3 of 24 unrelated patients (15%) with autosomal recessive nonsyndromic optic atrophy (arNSOA) and in 8 patients with autosomal recessive Wolfram syndrome (arWS) associated with diabetes mellitus and OA. Heterozygous mutations were found in 4 of 20 unrelated patients (20%) with autosomal dominant OA. The 4 WFS1-mutated patients of this latter group with hearing loss were diagnosed with autosomal dominant Wolfram-like syndrome (adWLS). Most patients had VA decrease, with logarithm of the minimum angle of resolution (logMAR) values lower in arWS than in arNSOA (1.530 vs. 0.440; P = 0.026) or adWLS (0.240; P = 0.006) but not differing between arNSOA and adWLS (P = 0.879). All patients had decreased RNFL thickness that was worse in arWS than in arNSOA (SD OCT, 35.50 vs. 53.80 μm; P = 0.018) or adWLS (TD-OCT, 45.84 vs. 59.33 μm; P = 0.049). The greatest difference was found in the inferior bundle. Visual acuity was negatively correlated with RNFL thickness (r = -0.89; P = 0.003 in SD OCT and r = -0.75; P = 0.01 in TD-OCT).
  
  
  
  WFS1 is a gene causing arNSOA. Patients with this condition had significantly less visual impairment than those with arWS. Thus systematic screening of WFS1 must be performed in isolated, sporadic, or familial optic atrophies.
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of Ophthalmology, CHRU, Montpellier, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Grenier
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France; INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.affiliation: Department of Ophthalmology, CHRU, Montpellier, France; Université Montpellier, Montpellier, France; INSERM U1061, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Daien
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Baudoin
authors.affiliation: INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France.
authors.forename: François
authors.initials: F
authors.lastname: Halloy
authors.affiliation: INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of ENT, CHRU, Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanchet
authors.affiliation: INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delettre
authors.affiliation: Ophthalmic Center, Montferrier le Lez, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Esmenjaud
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of Pediatric Neurology, CHRU, Montpellier, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.affiliation: PREMMi, INSERM U1083, CNRS 6214, Angers, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lenaers
authors.affiliation: Maladies Sensorielles Génétiques, CHRU, Montpellier, France; INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France. Electronic address: christian.hamel@inserm.fr.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009412:Nerve Fibers / Q000473:pathology; D009896:Optic Atrophy / Q000235:genetics* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012189:Retrospective Studies; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein