Genetic investigation in a four-generation Chinese family with congenital fibrosis of extraocular muscles and keratoconus
Qinghong Lin,
Xuejun Wang,
Xin Zhan,
Xiaoliao Peng,
Yan Wang,
Xingtao Zhou
Affiliations
Qinghong Lin
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200000, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Research Center of Ophthalmology and Optometry, Shanghai, 200000, China; Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000), Shanghai, 200000, China; Refractive Surgery Department, Bright Eye Hospital, Fuzhou, 350000, China
Xuejun Wang
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200000, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Research Center of Ophthalmology and Optometry, Shanghai, 200000, China; Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000), Shanghai, 200000, China
Xin Zhan
Refractive Surgery Department, Bright Eye Hospital, Fuzhou, 350000, China
Xiaoliao Peng
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200000, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Research Center of Ophthalmology and Optometry, Shanghai, 200000, China; Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000), Shanghai, 200000, China
Yan Wang
Refractive Surgery Department, Bright Eye Hospital, Fuzhou, 350000, China
Xingtao Zhou
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200000, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Research Center of Ophthalmology and Optometry, Shanghai, 200000, China; Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000), Shanghai, 200000, China; Corresponding author. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, No. 83 Fenyang Road, Xuhui District, Shanghai, 200000, China.
Here, we have reported the genetic and clinical characteristics of four generations of a family patient from China with congenital fibrosis of extraocular muscles 1 (CFEOM1) and keratoconus (KC). The history of diseases, clinical observations, and blood samples of all family members were collected. A total of 100 healthy participants were recruited as normal controls. The whole exome sequencing of the genomic DNA and polymerase chain reaction were performed on samples obtained from the controls and their family members to verify the gene variants. The functional analyses of the variants were performed by using different software. Two single nucleotide polymorphisms were detected in the proband and other patients in his families, including a heterozygous missense variation, g.39726207C > T (c.2860C > T, p.R954W, rs121912585), in the third highly conserved coiled-coil domain of KIF21A, and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in TGFBR2. The variant p.R954W in KIF21A was predicted to be pathogenic using software, whereas p.S46R in TGFBR2 was predicted to be of uncertain significance (VUS). Thus, KC might have occurred in the proband and his daughter because of a combination of genetic mutations and involuntary eye rubbing induced by CFEOM1. This is the first case of concomitant KC in a family having CFEOM1. Thus, the study provides new information about patients with KC having CFEOM1. Furthermore, the study suggests that attention should be paid to the early detection and diagnosis of KC in patients with CFEOM1.
