Joanna Grenier1, Isabelle Meunier2, Vincent Daien3, Corinne Baudoin4, François Halloy5, Béatrice Bocquet6, Catherine Blanchet7, Cécile Delettre6, Etienne Esmenjaud8, Agathe Roubertie9, Guy Lenaers10, Christian P Hamel11. 1. Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of Ophthalmology, CHRU, Montpellier, France. 2. Maladies Sensorielles Génétiques, CHRU, Montpellier, France; INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France. 3. Department of Ophthalmology, CHRU, Montpellier, France; Université Montpellier, Montpellier, France; INSERM U1061, Montpellier, France. 4. Maladies Sensorielles Génétiques, CHRU, Montpellier, France. 5. INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France. 6. INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; Université Montpellier, Montpellier, France. 7. Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of ENT, CHRU, Montpellier, France. 8. Ophthalmic Center, Montferrier le Lez, France. 9. Maladies Sensorielles Génétiques, CHRU, Montpellier, France; Department of Pediatric Neurology, CHRU, Montpellier, France. 10. PREMMi, INSERM U1083, CNRS 6214, Angers, France. 11. 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.
Abstract
PURPOSE: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment. DESIGN: Retrospective molecular genetic and clinical study. PARTICIPANTS: Patients with OA followed at a national referral center specialized in genetic sensory diseases. METHODS: 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. MAIN OUTCOME MEASURES: Mutation identification, VA values, and RNFL thickness in sectors. RESULTS: 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). CONCLUSIONS: 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.
PURPOSE: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment. DESIGN: Retrospective molecular genetic and clinical study. PARTICIPANTS: Patients with OA followed at a national referral center specialized in genetic sensory diseases. METHODS: 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. MAIN OUTCOME MEASURES: Mutation identification, VA values, and RNFL thickness in sectors. RESULTS: 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). CONCLUSIONS: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: Andrew T Chen; Lauren Brady; Dennis E Bulman; Arun N E Sundaram; Amadeo R Rodriguez; Edward Margolin; John S Waye; Mark A Tarnopolsky Journal: PLoS One Date: 2019-11-25 Impact factor: 3.240
Authors: Agnieszka Zmyslowska; Wojciech Fendler; Arleta Waszczykowska; Anna Niwald; Maciej Borowiec; Piotr Jurowski; Wojciech Mlynarski Journal: Acta Diabetol Date: 2017-08-30 Impact factor: 4.280