A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family.
Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Liping
L
Zhang
National Key Discipline of Pediatrics, Ministry of Education, Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Wei
W
Shi
Department of Urology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020 China.
Liming
L
Song
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Xiao
X
Zhang
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Lulu
L
Cheng
Zhejiang Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035 China.
Yanfang
Y
Wang
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Xianglian
X
Ge
Zhejiang Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035 China.
Wei
W
Li
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 China.
Wei
W
Zhang
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027 China.
Qingjie
Q
Min
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Zi-Bing
ZB
Jin
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Jia
J
Qu
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
Feng
F
Gu
D000328:Adult; D044466:Asian People; D001483:Base Sequence; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D005799:Genes, Dominant; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029241:Optic Atrophy, Autosomal Dominant / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion; D012867:Skin / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human