The clinical features of a known mendelian disease can occasionally be mimicked by the random co-occurrence of 2 different conditions in the same individual. We report a case in which whole-exome sequencing in a patient previously suspected to have Usher syndrome revealed disease-causing mutations in BBS1 and SLC26A4. This case illustrates how detailed and accurate clinical data are needed to interpret exome-scale genetic testing results.
A man in his late 30s was referred for evaluation of suspected Usher syndrome. As a toddler, he was diagnosed as having sensorineural hearing loss due to a Mondini malformation after computed tomography showed characteristic cochlear abnormalities (audiograms shown in Figure 1). A few years later, his parents noted that he began tripping over objects and having trouble seeing at night. Several years later, he was diagnosed as having retinitis pigmentosa and suspected to have Usher syndrome. At that time, his best-corrected visual acuity was 20/60 OD and 20/80 OS. By his early 20s, it had decreased to counting fingers OD and 20/800 OS. Aside from a paternal great-great-aunt with deafness, mutism, and normal vision, there were no other affected family members.
DeLuca AP, Weed MC, Haas CM, Halder JA, Stone EM. Apparent Usher Syndrome Caused by the Combination of BBS1-Associated Retinitis Pigmentosa and SLC26A4-Associated Deafness. JAMA Ophthalmol. 2015;133(8):967-968. doi:10.1001/jamaophthalmol.2015.1463