WFS1 in Optic Neuropathies: Mutation Findings in Nonsyndromic Optic Atrophy and Assessment of Clinical Severity

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• 作者：Joanna Grenier ; MD¹ ; ² ; Isabelle Meunier ; MD ; PhD¹ ; ³ ; ⁴ ; Vincent Daien ; MD ; PhD² ; ⁴ ; ⁵ ; Corinne Baudoin ; BS¹ ; Franç ; ois Halloy ; MS³ ; Bé ; atrice Bocquet ; PhD³ ; ⁴ ; Catherine Blanchet ; MD¹ ; ⁶ ; Cé ; cile Delettre ; PhD³ ; ⁴ ; Etienne Esmenjaud ; MD⁷ ; Agathe Roubertie ; MD ; PhD¹ ; ⁸ ; Guy Lenaers ; PhD⁹ ; Christian P. Hamel ; MD ; PhD¹ ; ³ ; ⁴ ; ^{christian.hamel@inserm.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：adWLS ; autosomal dominant Wolfram-like syndrome ; arNSOA ; autosomal recessive nonsyndromic optic atrophy ; arWS ; autosomal recessive Wolfram syndrome ; logMAR ; log10 of the minimal angle of resolution ; OA ; optic atrophy ; OCT ; optical coherence tomography ; OMIM ; Online Mendelian Inheritance in Man ; RNFL ; retinal nerve fiber layer ; SD ; spectral domain ; TD ; time domain ; VA ; visual acuity
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：123
• 期：9
• 页码：1989-1998
• 全文大小：1622 K

文摘

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.