Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall-Stickler syndrome spectrum

Abstract

Marshall-Stickler syndrome represents a spectrum of inherited connective tissue disorders affecting the ocular, auditory, and skeletal systems. The syndrome is caused by mutations in the COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 genes. In this study, we examined four Turkish families with Marshall-Stickler syndrome using whole-exome sequencing and identified one COL2A1 mutation and three COL11A1 mutations. Two of the COL11A1 mutations were novel. Our findings expand our knowledge of the COL11A1 mutational spectrum that causes Marshall-Stickler syndrome.

Figure 1

Physical appearance of the patients. (a, b) Case 1, age 1.5 years. Mild depression of the nasal bridge and micrognathia. (c) Case 2, age 1 month. Buphthalmic eyes, hypertelorism, bilateral epicanthus, flat face, depressed nasal bridge, short stubby nose, and micro-retrognathia. (d, e) Case 4, age 8.5 years. Proptotic eyes, flat face with mild frontal bossing, depressed nasal bridge, and short nose. (f, g) Case 3, age 9 months. Buphthalmic eyes, flat face with frontal bossing, midfacial hypoplasia, depressed nasal bridge, short nose with anteverted nares, long philtrum, and micro-retrognathia. (h–j) Case 3, age 9 years. (h, i) High-frontal area, big proptotic eyes, long palpebral fissures, depressed nasal bridge, short nose, long philtrum, irregular teeth order, micrognathia, and dry rough hairs. (j) Small hands with brachydactyly.