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Researchers have increased the number of patients with ARSG-Usher syndrome type IV to 31 cases and identified new genetic variants in this disease subtype.
An article published in Clinical Genetics highlights the role of the ARSG gene in Usher syndrome type IV and significantly increases the number of known patients with this rare disease subtype.
Usher syndrome, an inherited retinal disease that results in vision and hearing loss, is driven by various genes. The three major subtypes of this IRD, Usher syndrome types 1, 2, and 3, are determined based on the onset and severity of hearing loss, vestibular dysfunction, and the age of onset. So far, nine Usher syndrome genes have been implicated in these subtypes.
“In the past, biallelic variants in ARSG were tentatively assigned to cause ‘USH type IV’ or atypical Usher syndrome,” Miriam Bauwens, PhD, and colleagues wrote. “However, this classification [has been] under discussion, and classification as a new type of ‘deaf blindness’ syndrome was suggested recently. It is clear that ARSG-[Usher syndrome] can be considered an [ultra] rare subtype, with only 22 affected subjects described thus far.”
The findings published in Clinical Genetics expand the ARSG disease cohort to a total of 31 cases, according to the study results, which indicates that “the number will likely further increase and that variants in ARSG as a cause for Usher syndrome are underdiagnosed.”
Genetic Variants Identified in 13 Patients
Bauwens and colleagues identified new genetic variants in 11 of 13 patients. Patients 2, 5, 6, and 9-12 also had—in addition to the variants newly identified in the present study—variants identified in prior research (Table).
The findings expand the genetic landscape of ARSG-Usher syndrome type IV, according to Dr. Bauwens and colleagues. This expansion includes the identification of the new variants, the confirmation of previously identified variants, and the expanding of the number of known affected participants by approximately 30%. The small number of participants, may limit the generalizability of the results, the researchers noted.
“Our findings highlight that Usher syndrome type IV likely has been significantly underdiagnosed and emphasize the need to evaluate molecularly unresolved patients with Usher syndrome,” the researchers wrote. “As hearing loss is a late-onset feature in our cases, testing for ARSG variants should also be considered for patients with apparent isolated inherited retinal disease.”
