Clinical and Genetic Characteristics of Chinese Patients with Occult Macular Dystrophy

Purpose To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. Methods Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. Results The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6–51 years) and 27.0 years (range, 14–55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04–0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. Conclusions To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.

[1]  K. Tsubota,et al.  Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake Disease): East Asia Occult Macular Dystrophy Studies Report Number 1. , 2019, Ophthalmology.

[2]  Wei-Chi Wu,et al.  CLINICAL FEATURES IN A CASE OF OCCULT MACULAR DYSTROPHY WITH RP1L1 MUTATION , 2017, Retinal cases & brief reports.

[3]  E. Zrenner,et al.  Phenotype Variations Caused by Mutations in the RP1L1 Gene in a Large Mainly German Cohort. , 2018, Investigative ophthalmology & visual science.

[4]  K. Tsunoda,et al.  Parafoveal Photoreceptor Abnormalities in Asymptomatic Patients With RP1L1 Mutations in Families With Occult Macular Dystrophy. , 2017, Investigative ophthalmology & visual science.

[5]  Feng-Juan Gao,et al.  Next-Generation Sequencing-Aided Rapid Molecular Diagnosis of Occult Macular Dystrophy in a Chinese Family , 2017, Front. Genet..

[6]  C. Möller,et al.  Putative digenic inheritance of heterozygous RP1L1 and C2orf71 null mutations in syndromic retinal dystrophy , 2017, Ophthalmic genetics.

[7]  D. Sarraf,et al.  OCCULT MACULAR DYSTROPHY WITH MUTATIONS IN THE RP1L1 AND KCNV2 GENES , 2017, Retinal cases & brief reports.

[8]  K. Tsubota,et al.  Novel RP1L1 Variants and Genotype-Photoreceptor Microstructural Phenotype Associations in Cohort of Japanese Patients With Occult Macular Dystrophy. , 2016, Investigative ophthalmology & visual science.

[9]  K. Tsunoda,et al.  Occult macular dystrophy , 2015, Japanese Journal of Ophthalmology.

[10]  K. Yamaki,et al.  Cone Dystrophy in Patient with Homozygous RP1L1 Mutation , 2015, BioMed research international.

[11]  Seong Joon Ahn,et al.  Multimodal imaging of occult macular dystrophy. , 2013, JAMA ophthalmology.

[12]  G. Holder,et al.  RP1L1 Variants are Associated with a Spectrum of Inherited Retinal Diseases Including Retinitis Pigmentosa and Occult Macular Dystrophy , 2013, Human mutation.

[13]  A. Mizota,et al.  A new mutation in the RP1L1 gene in a patient with occult macular dystrophy associated with a depolarizing pattern of focal macular electroretinograms , 2012, Molecular vision.

[14]  K. Tsunoda,et al.  Fundus autofluorescence in autosomal dominant occult macular dystrophy. , 2011, Archives of ophthalmology.

[15]  S. Tsuji,et al.  Dominant mutations in RP1L1 are responsible for occult macular dystrophy. , 2010, American journal of human genetics.

[16]  S. Daiger,et al.  Essential and Synergistic Roles of RP1 and RP1L1 in Rod Photoreceptor Axoneme and Retinitis Pigmentosa , 2009, The Journal of Neuroscience.

[17]  G. Eichele,et al.  The DCX Superfamily 1: Common and Divergent Roles for Members of the Mouse DCX Superfamily , 2006, Cell cycle.

[18]  Jian Zuo,et al.  Characterization of RP1L1, a highly polymorphic paralog of the retinitis pigmentosa 1 (RP1) gene. , 2003, Molecular vision.

[19]  Sandro Banfi,et al.  Identification and characterisation of the retinitis pigmentosa 1-like1 gene (RP1L1): a novel candidate for retinal degenerations , 2003, European Journal of Human Genetics.

[20]  M. F. Escaño,et al.  Immunohistological findings in a patient with unusual late onset manifestation of ligneous conjunctivitis , 1999, The British journal of ophthalmology.

[21]  Y. Shiose,et al.  Hereditary macular dystrophy without visible fundus abnormality. , 1989, American journal of ophthalmology.