Research Papers: Chromosome:

Genetic identification and molecular modeling characterization reveal a novel PROM1 mutation in Stargardt4-like macular dystrophy

Saber Imani, Jingliang Cheng, Marzieh Dehghan Shasaltaneh, Chunli Wei, Lisha Yang, Shangyi Fu, Hui Zou, Md. Asaduzzaman Khan, Xianqin Zhang, Hanchun Chen, Dianzheng Zhang, Chengxia Duan, Hongbin Lv, Yumei Li, Rui Chen and Junjiang Fu _

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Oncotarget. 2018; 9:122-141. https://doi.org/10.18632/oncotarget.22343

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Saber Imani1,2,3,*, Jingliang Cheng2,*, Marzieh Dehghan Shasaltaneh4,5,*, Chunli Wei2,6, Lisha Yang2, Shangyi Fu7,8, Hui Zou1,2, Md. Asaduzzaman Khan2, Xianqin Zhang2, Hanchun Chen9, Dianzheng Zhang10, Chengxia Duan11, Hongbin Lv11, Yumei Li8, Rui Chen8 and Junjiang Fu1,2,6

1 Hunan Normal University Medical College, Changsha, Hunan, China

2 Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China

3 Chemical Injuries Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran

4 Laboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

5 Laboratory of Systems Biology and Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

6 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China

7 The Honors College, University of Houston, Houston, TX, USA

8 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

9 Department of Biochemistry, School of Life Sciences & the State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China

10 Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA

11 Department of Ophthalmology, First Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China

* These authors have contributed equally to this work

Correspondence to:

Junjiang Fu, email:

Keywords: stargardt disease-4 (STGD4); next generation sequencing; PROM1; missense mutation; molecular modeling

Received: June 14, 2017 Accepted: August 26, 2017 Published: November 09, 2017


Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c.734T>C (p.L245P) in the PROM1 gene. Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loop-helix leucine zipper domain. Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD. Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD.

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