Abstract
Purpose
This study is to summarize the concurrent keratoconus (KC) and granular corneal dystrophy (GCD) phenotype and identify the underlying genetic cause in a 23-year-old male patient.
Methods
A detailed family history and clinical data from the patient and his parents were collected by ophthalmologic examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing.
Results
The proband was clinically diagnosed as a case of concurrent KC and GCD, which is a very rare presentation. His father and grandmother were diagnosed as GCD in both eyes. There was no character of KC in his father’s and grandmother’s eyes. A heterozygous TGFBI mutation in exon 4 (c.370G > A) was identified in the proband, which was predicted to generate a missense mutation (p.R124H). The mutation also existed in his father and grandmother. A heterozygous KRT12 mutation in exon 8 (c.1456-1457ins GTA) was identified in the proband, which was predicted to generate an insert mutation and created a premature termination codon. The mutation did not exist in his father and grandmother. The two mutations did not exist in his mother and 200 unrelated normal controls.
Conclusions
KC can co-exist with GCD. The missense mutation (c.370G > A) in the TGFBI gene and insert mutation (c.1456-1457ins GAT) in the KRT12 gene were identified in a 23-year-old male patient with concurrent KC and GCD.
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Acknowledgements
We would like to express our gratitude to the participating family. For the data set used to filter variants, we thank the Single Nucleotide Polymorphism database, 1000 genome project, HapMap 8 database, and the YH database.
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The National Natural Science Foundation of China provided financial support in the form of funds from the National Natural Science Foundation of China (81300742). The Department of Science Technology of Shandong Shi Nan District provided financial support in the form of the Science and Technology Foundation of Shi Nan District, Qingdao, Shandong Province, China (2015–06-020-YY). The sponsor had no role in the design or conduct of this research.
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All authors certify that they 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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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Du, X., Chen, P. & Sun, D. Mutation analysis of TGFBI and KRT12 in a case of concomitant keratoconus and granular corneal dystrophy. Graefes Arch Clin Exp Ophthalmol 255, 1779–1786 (2017). https://doi.org/10.1007/s00417-017-3699-5
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DOI: https://doi.org/10.1007/s00417-017-3699-5