Identification of novel PROM1 mutations responsible for autosomal recessive maculopathy with rod-cone dystrophy

  • Jian Liang
  • Xiangjun She
  • Jieqiong Chen
  • Yuanqi Zhai
  • Yang Liu
  • Kairong Zheng
  • Yuanyuan Gong
  • Hong Zhu
  • Xueting Luo
  • Xiaodong Sun



To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease.


Ophthalmic examinations were performed for the family and the peripheral blood samples were collected for whole exome sequencing. The mutated sequences of PROM1 gene were cloned and expressed in cultured cell lines after transient transfection followed by analysis with confocal microscopy and bridge-PCR.


We reported that two patients, brothers in a family, were diagnosed with macular and rod-cone dystrophy. Phenotypically, both patients experience progressive visual impairment and nyctalopia. The fundus examination showed macular and choroid dystrophy with pigment deposits in the macular region. Functionally, photoreceptor response to electrophysiological stimulation was significantly compromised with more severe decline in rods. Genetic analysis by whole exome sequencing revealed two novel compound heterogeneous point mutations in PROM1 gene that co-segregate with patients in an autosomal recessive manner. Specifically, the c.C1902G(p.Y634X) nonsense mutation results in a truncated, labile, and mislocalized protein, while the c.C1682+3A>G intronic mutation disrupts messenger RNA splicing.


Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.


Hereditary retinal disease Macular and rod-cone dystrophy PROM1 



We are grateful to the family for their participation in the study.


This work was funded by the National Science and Technology Major Project for Drug Discovery of the Ministry of Science and Technology of China (2018ZX09301029-001), National Natural Science Foundation of China (81700828), National Key R&D Program of China (2017YFA0105300), Program for Eastern Young Scholar at Shanghai Institutions of Higher Learning (QD2016003), Shanghai Rising-Star Program (17QA1402800), Shanghai Pujiang Program (16PJ1408500), Frontier Project of Hospital Development Center (SHDC12016105), and Chenxing Project from Shanghai Jiao Tong University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were approved by the medical ethics committee of Shanghai General Hospital (Shanghai First People’s Hospital) Affiliated to Shanghai Jiao Tong University (No. 2013KY096) and was conducted in accordance with the Declaration of Helsinki of the World Medical Association.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Shanghai Key Laboratory of Fundus DiseasesShanghaiChina
  3. 3.Shanghai Engineering Center for Visual Science and PhotomedicineShanghaiChina

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