Joshua L Hagedorn, Taylor M Dunn, Sajag Bhattarai, Carrie Stephan, Katherine D Mathews, Wanda Pfeifer, Arlene V Drack
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Previous studies have characterized electroretinogram findings of dystroglycanopathy mouse models but have not been reported in humans.</p><p><strong>Purpose: </strong>This study set out to characterize the electroretinogram in eight participants with LGMDR9.</p><p><strong>Methods: </strong>Eight participants were recruited from an ongoing dystroglycanopathy natural history study at the University of Iowa (NCT00313677). Inclusion criteria for the current study were children and adults > 6 years old with confirmed LGMDR9. Age similar controls were identified from our electrophysiology service normative control database. Full-field electroretinograms were recorded using ISCEV standards. Six of the eight participants underwent light-adapted ON/OFF testing.</p><p><strong>Results: </strong>The electronegative electroretinogram was not seen in any participants with LGMDR9. An unusual sawtooth pattern in the 30 Hz flicker with faster rise than descent was noted in all 8 participants. Our cases showed a decreased b-wave amplitude in light-adapted ON responses (p = 0.011) and decreased d-wave amplitude in light-adapted OFF responses (p = 0.015). Decreased b-wave amplitude in light-adapted 3.0 testing (p = 0.015) and decreased flicker ERG amplitudes were also detected (p = 0.0018). Additionally, compared to controls, participants with LGMDR9 had decreased a-wave amplitudes on dark-adapted 10 testing (p = 0.026).</p><p><strong>Conclusions: </strong>Abnormal ON/OFF bipolar cell responses and sawtooth 30 Hz flicker waveforms on full-field electroretinogram may be specific for LGMDR9. If confirmed in a larger population and if related to disease stage, these tests are potential biomarkers which could be useful as endpoints in clinical treatment trials.</p>","PeriodicalId":11207,"journal":{"name":"Documenta Ophthalmologica","volume":"146 1","pages":"7-16"},"PeriodicalIF":2.6000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171413/pdf/","citationCount":"0","resultStr":"{\"title\":\"Electroretinogram abnormalities in FKRP-related limb-girdle muscular dystrophy (LGMDR9).\",\"authors\":\"Joshua L Hagedorn, Taylor M Dunn, Sajag Bhattarai, Carrie Stephan, Katherine D Mathews, Wanda Pfeifer, Arlene V Drack\",\"doi\":\"10.1007/s10633-022-09909-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Dystroglycanopathies are a heterogeneous group of membrane-related muscular dystrophies. The dystroglycanopathy phenotype includes a spectrum of severity ranging from severe congenital muscular dystrophy to adult-onset limb-girdle muscular dystrophy (LGMD). LGMDR9 is a dystroglycanopathy caused by mutations in the FKRP gene. Previous studies have characterized electroretinogram findings of dystroglycanopathy mouse models but have not been reported in humans.</p><p><strong>Purpose: </strong>This study set out to characterize the electroretinogram in eight participants with LGMDR9.</p><p><strong>Methods: </strong>Eight participants were recruited from an ongoing dystroglycanopathy natural history study at the University of Iowa (NCT00313677). Inclusion criteria for the current study were children and adults > 6 years old with confirmed LGMDR9. Age similar controls were identified from our electrophysiology service normative control database. Full-field electroretinograms were recorded using ISCEV standards. Six of the eight participants underwent light-adapted ON/OFF testing.</p><p><strong>Results: </strong>The electronegative electroretinogram was not seen in any participants with LGMDR9. An unusual sawtooth pattern in the 30 Hz flicker with faster rise than descent was noted in all 8 participants. Our cases showed a decreased b-wave amplitude in light-adapted ON responses (p = 0.011) and decreased d-wave amplitude in light-adapted OFF responses (p = 0.015). Decreased b-wave amplitude in light-adapted 3.0 testing (p = 0.015) and decreased flicker ERG amplitudes were also detected (p = 0.0018). Additionally, compared to controls, participants with LGMDR9 had decreased a-wave amplitudes on dark-adapted 10 testing (p = 0.026).</p><p><strong>Conclusions: </strong>Abnormal ON/OFF bipolar cell responses and sawtooth 30 Hz flicker waveforms on full-field electroretinogram may be specific for LGMDR9. If confirmed in a larger population and if related to disease stage, these tests are potential biomarkers which could be useful as endpoints in clinical treatment trials.</p>\",\"PeriodicalId\":11207,\"journal\":{\"name\":\"Documenta Ophthalmologica\",\"volume\":\"146 1\",\"pages\":\"7-16\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171413/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Documenta Ophthalmologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10633-022-09909-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/11/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Documenta Ophthalmologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10633-022-09909-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/18 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：肌营养不良症是一组与膜相关的肌肉营养不良症。肌营养不良症的表型包括从严重的先天性肌营养不良症到成人发病的肢腰肌营养不良症（LGMD）等各种严重程度。LGMDR9 是一种由 FKRP 基因突变引起的肌营养不良症。以前的研究已经描述了肌营养不良症小鼠模型的视网膜电图结果，但还没有关于人类视网膜电图的报道。目的：本研究旨在描述八名 LGMDR9 患者的视网膜电图特征：从爱荷华大学正在进行的肌营养不良症自然史研究（NCT00313677）中招募了八名参与者。本次研究的纳入标准是年龄大于 6 岁、确诊为 LGMDR9 的儿童和成人。年龄相仿的对照组是从我们的电生理学服务常模对照数据库中确定的。采用 ISCEV 标准记录全场视网膜电图。八名参与者中有六名接受了光适应开/关测试：结果：所有 LGMDR9 患者均未出现电负性视网膜电图。所有 8 名患者的 30 Hz 闪烁图中都出现了不寻常的锯齿波模式，且上升速度快于下降速度。我们的病例显示，光适应 ON 反应中的 b 波振幅减小（p = 0.011），光适应 OFF 反应中的 d 波振幅减小（p = 0.015）。在光适应 3.0 测试中还检测到 b 波振幅降低（p = 0.015）和闪烁 ERG 振幅降低（p = 0.0018）。此外，与对照组相比，LGMDR9 患者在暗适应 10 测试中的 a 波振幅降低（p = 0.026）：结论：全场视网膜电图上异常的ON/OFF双极细胞反应和30赫兹锯齿闪烁波形可能是LGMDR9的特异性表现。如果在更大的人群中得到证实，并且与疾病分期相关，这些测试将成为潜在的生物标志物，可作为临床治疗试验的终点。
Electroretinogram abnormalities in FKRP-related limb-girdle muscular dystrophy (LGMDR9).
Background: Dystroglycanopathies are a heterogeneous group of membrane-related muscular dystrophies. The dystroglycanopathy phenotype includes a spectrum of severity ranging from severe congenital muscular dystrophy to adult-onset limb-girdle muscular dystrophy (LGMD). LGMDR9 is a dystroglycanopathy caused by mutations in the FKRP gene. Previous studies have characterized electroretinogram findings of dystroglycanopathy mouse models but have not been reported in humans.
Purpose: This study set out to characterize the electroretinogram in eight participants with LGMDR9.
Methods: Eight participants were recruited from an ongoing dystroglycanopathy natural history study at the University of Iowa (NCT00313677). Inclusion criteria for the current study were children and adults > 6 years old with confirmed LGMDR9. Age similar controls were identified from our electrophysiology service normative control database. Full-field electroretinograms were recorded using ISCEV standards. Six of the eight participants underwent light-adapted ON/OFF testing.
Results: The electronegative electroretinogram was not seen in any participants with LGMDR9. An unusual sawtooth pattern in the 30 Hz flicker with faster rise than descent was noted in all 8 participants. Our cases showed a decreased b-wave amplitude in light-adapted ON responses (p = 0.011) and decreased d-wave amplitude in light-adapted OFF responses (p = 0.015). Decreased b-wave amplitude in light-adapted 3.0 testing (p = 0.015) and decreased flicker ERG amplitudes were also detected (p = 0.0018). Additionally, compared to controls, participants with LGMDR9 had decreased a-wave amplitudes on dark-adapted 10 testing (p = 0.026).
Conclusions: Abnormal ON/OFF bipolar cell responses and sawtooth 30 Hz flicker waveforms on full-field electroretinogram may be specific for LGMDR9. If confirmed in a larger population and if related to disease stage, these tests are potential biomarkers which could be useful as endpoints in clinical treatment trials.
期刊介绍：
Documenta Ophthalmologica is an official publication of the International Society for Clinical Electrophysiology of Vision. The purpose of the journal is to promote the understanding and application of clinical electrophysiology of vision. Documenta Ophthalmologica will publish reviews, research articles, technical notes, brief reports and case studies which inform the readers about basic and clinical sciences related to visual electrodiagnosis and means to improve diagnosis and clinical management of patients using visual electrophysiology. Studies may involve animals or humans. In either case appropriate care must be taken to follow the Declaration of Helsinki for human subject or appropriate humane standards of animal care (e.g., the ARVO standards on Animal Care and Use).
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