Mild retinitis pigmentosa, including sector retinitis pigmentosa associated with 2 pathogenic variants in .

BACKGROUND

Biallelic pathogenic variants in can cause Usher syndrome type I (USH1), typically characterized by sensorineural hearing loss, variable vestibular areflexia, and a progressive form of rod-cone dystrophy. While missense variants in can cause DFNB12 deafness, other variants can affect the cadherin 23 function, more severely causing Usher syndrome type I D. The main purpose of our study is to describe the genotypes and phenotypes of patients with mild retinitis pigmentosa (RP), including sector RP with two pathogenic variants in .

MATERIALS AND METHODS

Clinical examination included medical history, comprehensive ophthalmologic examination, and multimodal retinal imaging, and in case 1 and 2, full-field electroretinography (ERG). Genetic analysis was performed in all cases, and segregation testing of proband relatives was performed in case 1 and 3.

RESULTS

Three unrelated cases presented with variable clinical phenotype for USH1 and were found to have two pathogenic variants in , with missense variant, c.5237 G > A: p.Arg1746Gln being common to all. All probands had mild to profound hearing loss. Case 1 and 3 had mild RP with mid peripheral and posterior pole sparing, while case 2 had sector RP. ERG results were consistent with the marked loss of retinal function in both eyes at the level of photoreceptor in case 1 and case 2, with normal peak time in the former.

CONCLUSION

Patients harbouring c.5237 G > A: p.Arg1746Gln variants in can present with a mild phenotype including sector RP. This can aid in better genetic counselling and in prognostication.