Genetic investigation in a four-generation Chinese family with congenital fibrosis of extraocular muscles and keratoconus.

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 , and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in . The variant p.R954W in was predicted to be pathogenic using software, whereas p.S46R in 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.