Abstract
Purpose :
To determine the utility of the new 248 gene panel in providing a molecular diagnosis to patients with inherited retinal diseases.
Methods :
46 patients (23 female, 23 male) underwent next-generation sequencing with the expanded ID YOUR IRD panel of 248 genes (Invitae-Spark Therapeutics Initiative). Genetic (Blood or saliva) samples were obtained during patients’ visits at the WVU Eye Institute Retina Clinic. Forty-three patients were Caucasian, 3 were African American. Average age was 48 years (3-83). We reviewed visual acuity, fundoscopy with autofluorescence imaging, OCT, ERG, family history, and prior genetic results (ARVO 2019, abstract ID#: 2928 – A0211). Results were disclosed to the patients during a follow up phone conversation by the ophthalmologist. All patients were encouraged to consult a genetic counselor, provided by the sponsoring company or WVU, and arrange variant testing where indicated.
Results :
Genetic testing provided a confirmatory molecular diagnosis in 13 patients (28.2%). Five patients had pathogenic mutations in FZD4, IMPDH1, PRPH2, RP1, and RHO with autosomal dominant inheritance patterns. Seven patients had autosomal recessive disease, with positive results for homozygous mutations in ABGL5(1), BBS1(1), CNGB1(1), NPHP1(1), USH2A (1), and heterozygous mutations in ABCA4, and USH2A. One patient had a hemizygous mutation in RP2 with X-linked retinitis pigmentosa. Eleven patients (23.9%) were identified as carriers of pathogenic genes. 18 patients (39.1%) had undergone previous genetic testing, which had yielded negative results. Among these patients, 9 (50%) obtained clinically relevant results. Five obtained a new pathogenic molecular diagnosis and 4 were found to be carriers of heterozygous pathogenic variants. No patients contacted an off-site genetic counselor or agreed to receive additional saliva kits or complete portal information at home. The BBS patient was referred to WVU genetics and five family members consented to have variant testing.
Conclusions :
Genetic testing in individuals with IRD allowed us to provide more personalized care to our patients. This rural cohort demanded local professional assistance for all sample collection and results reception and was not interested in off-site counseling. The 248 gene panel detected IRD undetected by earlier panels. More extensive panels may detect a larger number of IRDs.
This is a 2020 ARVO Annual Meeting abstract.