Exome sequencing in retinal dystrophy patients reveals a novel candidate gene ER membrane protein complex subunit 3
Yan-Ping Li,
Ren-Juan Shen,
You-Min Cheng,
Qingqing Zhao,
Kangxin Jin,
Zi-Bing Jin,
Shaodan Zhang
Affiliations
Yan-Ping Li
Laboratory for Stem Cell & Retinal Regeneration, The Eye Hospital, Basic Medical College, Wenzhou Medical University, Wenzhou, 325027, China
Ren-Juan Shen
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China
You-Min Cheng
Laboratory for Stem Cell & Retinal Regeneration, The Eye Hospital, Basic Medical College, Wenzhou Medical University, Wenzhou, 325027, China
Qingqing Zhao
Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310030, China
Kangxin Jin
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China; Corresponding author.
Zi-Bing Jin
Laboratory for Stem Cell & Retinal Regeneration, The Eye Hospital, Basic Medical College, Wenzhou Medical University, Wenzhou, 325027, China; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100730, China; Corresponding author. Laboratory for Stem Cell & Retinal Regeneration, The Eye Hospital, Basic Medical College, Wenzhou Medical University, Wenzhou, 325027, China
Shaodan Zhang
The Eye Hospital of Wenzhou Medical University, National Clinical Research Center for Ocular Diseases, Glaucoma Research Institute of Wenzhou Medical University, Wenzhou, 325027, China; Corresponding author.
Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.
