Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population.


Journal

American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745

Informations de publication

Date de publication:
09 2020
Historique:
received: 15 05 2020
revised: 26 07 2020
accepted: 27 07 2020
pubmed: 21 8 2020
medline: 3 6 2021
entrez: 22 8 2020
Statut: ppublish

Résumé

Variants in the PROM1 gene are associated with cone (-rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1-associated retinal disorder (PROM1-RD) in a nationwide cohort. A literature review of PROM1-RD in the Japanese population was also performed. The median age at onset/examination of 10 patients was 31.0 (range, 10-45)/44.5 (22-73) years. All 10 patients showed atrophic macular changes. Seven patients (70.0%) had spared fovea to various degrees, approximately half of whom had maintained visual acuity. Generalized cone (-rod) dysfunction was demonstrated in all nine subjects with available electrophysiological data. Three PROM1 variants were identified in this study: one recurrent disease-causing variant (p.Arg373Cys), one novel putative disease-causing variant (p.Cys112Arg), and one novel variant of uncertain significance (VUS; p.Gly53Asp). Characteristic features of macular atrophy with generalized cone-dominated retinal dysfunction were shared among all 10 subjects with PROM1-RD, and the presence of foveal sparing was crucial in maintaining visual acuity. Together with the three previously reported variants [p.R373C, c.1551+1G>A (pathogenic), p.Asn580His (likely benign)] in the literature of Japanese patients, one prevalent missense variant (p.Arg373Cys, 6/9 families, 66.7%) detected in multiple studies was determined in the Japanese population, which was also frequently detected in the European population.

Identifiants

pubmed: 32820593
doi: 10.1002/ajmg.c.31826
doi:

Substances chimiques

AC133 Antigen 0
PROM1 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

656-674

Informations de copyright

© 2020 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.

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Auteurs

Kaoru Fujinami (K)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.

Akio Oishi (A)

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Lizhu Yang (L)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Gavin Arno (G)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.
North East Thames Regional Genetics Service, UCL Great Ormond Street Institute of Child Health, Great Ormond Street NHS Foundation Trust, London, UK.

Nikolas Pontikos (N)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.

Kazutoshi Yoshitake (K)

Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Yu Fujinami-Yokokawa (Y)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
UCL Institute of Ophthalmology, London, UK.
Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan.
Division of Public Health, Yokokawa Clinic, Suita, Japan.

Xiao Liu (X)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Takaaki Hayashi (T)

Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.

Satoshi Katagiri (S)

Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.

Kei Mizobuchi (K)

Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.

Atsushi Mizota (A)

Department of Ophthalmology, Teikyo University, Tokyo, Japan.

Kei Shinoda (K)

Department of Ophthalmology, Teikyo University, Tokyo, Japan.
Department of Ophthalmology, Saitama Medical University, Saitama, Japan.

Natsuko Nakamura (N)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Ophthalmology, Teikyo University, Tokyo, Japan.
Department of Ophthalmology, The University of Tokyo, Tokyo, Japan.

Toshihide Kurihara (T)

Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Kazuo Tsubota (K)

Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Yozo Miyake (Y)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Aichi Medical University, Nagakute, Japan.
Next vision, Kobe Eye Center, Hyogo, Japan.

Takeshi Iwata (T)

Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Akitaka Tsujikawa (A)

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Kazushige Tsunoda (K)

Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

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