Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment

• DOI: 10.1007/s00439-021-02303-1
• Publication Date: 2021-06-19T23:04:35Z
• Authors: Paulina Bahena; Narsis Daftarian; Reza Maroofian; Paola Linares; Daniel Villalobos; Mehraban Mirrahimi; Aboulfazl Rad; Julia Doll; Michaela A. H. Ho...; Asuman Koparir; Tabea Röder; Seungbin Han; Hamideh Sabbaghi; Hamid Ahmadieh; Hassan Behboudi; Cristina Villanue...; Vianney Cortés-Go...; Rocio Zamora-Ortiz; Susanne Kohl; Laura Kuehlewein; Hossein Darvish; Elham Alehabib; Maria de la Luz A...; Fatemeh Suri; Barbara Vona; Thomas Haaf
• Keywords: Proband; Usher syndrome; Dystrophy

Abstract Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically genetically heterogeneous. Moreover, several conditions with phenotypes overlapping syndrome have been described. This makes molecular diagnosis deaf–blindness challenging. Here, we performed exome sequencing analysis on 7 Mexican 52 Iranian probands retinal degeneration impairment (without intellectual disability). Clinical assessment involved ophthalmological examination loss questionnaire. frequently due to biallelic variants in MYO7A (USH1B 16 probands), USH2A (17 ADGRV1 (USH2C was diagnosed 44 59 (75%) unrelated probands. Almost half identified were novel. Nine (15%) displayed other genetic entities dual sensory including Alström (3 patients), cone-rod dystrophy 1 (2 Heimler (1 patient). Unexpected findings included one proband each Scheie coenzyme Q10 deficiency, pseudoxanthoma elasticum. In four probands, three cases, either modified/aggravated or caused by distinct genes associated and/or loss. The overall diagnostic yield whole our deaf–blind cohort 92%. Two (3%) partially solved only 3 (5%) remained without any diagnosis. many important guide counseling, support prognostic outcomes decisions currently available evolving treatment modalities.