Xianli Du1, Peng Chen2,3, Dapeng Sun1. 1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China. 2. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China. chenpeng599205@126.com. 3. Department of Human Anatomy, Histology and Embryology, Qingdao University, Qingdao, China. chenpeng599205@126.com.
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.
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.
Authors: W W Kao; C Y Liu; R L Converse; A Shiraishi; C W Kao; M Ishizaki; T Doetschman; J Duffy Journal: Invest Ophthalmol Vis Sci Date: 1996-12 Impact factor: 4.799
Authors: Federico A Cremona; Faris R Ghosheh; Christopher J Rapuano; Ralph C Eagle; Kristin M Hammersmith; Peter R Laibson; Brandon D Ayres; Elisabeth J Cohen Journal: Cornea Date: 2009-02 Impact factor: 2.651
Authors: Wayne I L Davies; Susan M Downes; Josephine K Fu; Morag E Shanks; Richard R Copley; Stefano Lise; Simon C Ramsden; Graeme C M Black; Kate Gibson; Russell G Foster; Mark W Hankins; Andrea H Németh Journal: Genet Med Date: 2012-07-12 Impact factor: 8.822