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Clinical and genetic characteristics of Leber congenital amaurosis with novel mutations in known genes based on a Chinese eastern coast Han population

  • Pediatrics
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To study the genotype-phenotype characteristics of Leber congenital amaurosis (LCA) in the Chinese eastern coast Han population.

Methods

Children with strictly defined LCA with novel mutations of known LCA genes identified by targeted next-generation sequencing (NGS) and a prediction of pathogenicity (in silico) were included in this study (2013–2015). Mutations were confirmed using Sanger sequencing and segregation analysis. The clinical findings were recorded, including visual function, refractive error, fundus changes, and electroretinograms (ERGs). Spectral-domain optical coherence tomography (SD-OCT) examination, fundus fluorescein angiography (FFA), and ultra-wide field scanning laser ophthalmoscopy (UWF SLO) were performed on children when available.

Results

A total of 65 patients underwent NGS for mutation screening and 45 patients were identified as carrying known LCA genes. Of these, 36(80 %) children harbored novel mutations, and they were all from the eastern coast of China. A total of 50 novel variants were identified, which covered 15 known LCA genes. GUCY2D (17 %), CEP290 (14 %), NMNAT1 (14 %), AIPL1 (11 %) and RPGRIP1 (11 %) were the five most frequently mutated genes with novel mutations. A total of four (11 %) patients with AIPL1 mutations harbored the same novel mutated allele (c.C241T p.Q81X), which was homozygous in patients 1 and 2. Unusual manifestations were detected in patient 16 who had novel mutations in CRB1 with a dense proliferative membrane adhering to the posterior retina of the right eye with numerous fine glistening crystals spreading over the retina of both eyes. Ten (40 %) of the 25 available patients who underwent SD-OCT showed a normal macular appearance using fundus photography but an abnormal macular structure using OCT imaging, most of whom presented with a thickened fovea with maldevelopment of the inner and outer retinal laminae.

Conclusions

There may be a high frequency of AIPL1 novel mutations and a founder mutation of p.Q81X in the Chinese eastern coast Han population. Our findings of specific features in this population broaden the spectrum of novel mutations and the phenotype of LCA with ethnic and regional variations. Fundus multimodality imaging may help guide comprehensive assessments for patients with LCA.

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Acknowledgments

We sincerely thank all the patients and their families for their participation. We thank Hui Wang from Baylor College of Medicine for her help on the molecular study.

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Authors and Affiliations

  1. Department of Ophthalmology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China

    Shiyuan Wang, Qi Zhang, Xiang Zhang, Zhaoyang Wang & Peiquan Zhao

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  1. Shiyuan Wang
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  2. Qi Zhang
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  3. Xiang Zhang
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Corresponding author

Correspondence to Peiquan Zhao.

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Funding

Shanghai Health Bureau provided financial support in the form of “Molecular Genetics Study of Leber Congenital Amaurosis by Whole-exome Sequencing in Chinese People” Funding(XBR20111060). The sponsor had no role in the design or conduct of this research.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Xinhua Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

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

Conflict of interest

All authors declare that they have no conflict of interests to state. All authors have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Wang, S., Zhang, Q., Zhang, X. et al. Clinical and genetic characteristics of Leber congenital amaurosis with novel mutations in known genes based on a Chinese eastern coast Han population. Graefes Arch Clin Exp Ophthalmol 254, 2227–2238 (2016). https://doi.org/10.1007/s00417-016-3428-5

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  • DOI: https://doi.org/10.1007/s00417-016-3428-5

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