Genetic testing and diagnosis of inherited retinal diseases

Lam, Byron L.; Leroy, Bart P.; Black, Graeme; Ong, Tuyen; Trzupek, Karmen M

doi:10.1186/s13023-021-02145-0

Cited by 39 publications

(32 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These tests will be helpful in future studies to elucidate the disease mechanisms. Additionally, genetic testing technology has drastically improved over the past decade [ 34 ]. Consequently, the development of genomic databases and other resources that are publicly accessible revolutionized our ability to interpret genetic testing data.…”

Section: Discussionmentioning

confidence: 99%

Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series

Jimenez

Procopio

Thuma

et al. 2022

IJMS

View full text Add to dashboard Cite

Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients’ disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series

Jimenez

Procopio

Thuma

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…More efforts are required to increase awareness of XLRP and underline the importance of genetic testing to healthcare providers and regulatory authorities, which may have limited knowledge of this rare disorder. The collaboration of ophthalmologists and general practitioners with other experts, including genetic counselors and retina specialists, is encouraged for optimal decision-making and accurate diagnoses of XLRP and other inherited eye diseases [12,22]. Patients with inherited retinal disorders also vary regarding their understanding of genetic testing, but the majority respond that they would be likely to undergo genetic testing if it was offered [23].…”

Section: Discussion and Clinical Implicationsmentioning

confidence: 99%

Impacts of X-linked retinitis pigmentosa and patient pathways in European countries: results from the cross-sectional EXPLORE XLRP-1 physician survey

Pungor

Lee

Denee

et al. 2022

Preprint

View full text Add to dashboard Cite

Retina specialists (n = 20) and geneticists (n = 5) in France, Germany, Italy, Spain, and the United Kingdom were interviewed to provide insights on real-world patients (n = 80) with X-linked retinitis pigmentosa (XLRP). Survey respondents reported that their patients with XLRP often required assistance as their independence decreased over time, from 37% being “completely autonomous” at diagnosis (2% were “completely dependent” on family/friends), to 23% at their most recent consultation (10% were “completely dependent”). At their last visit, 45% of patients were active in the workforce. Workforce participation was related to independence/autonomy; 67% of “completely autonomous” patients were active, compared with 13% of “completely dependent” patients. The pathways by which patients with XLRP in these five countries visit retina specialists and geneticists are complex, lengthy, and vary considerably by country. Physicians reported high usage of genetic testing to confirm XLRP diagnosis (77.5%); however, long waiting times for test results account for incomplete uptake, especially among older patients. Teleconsultations and remote management have emerged as potential solutions for monitoring patients during the COVID-19 pandemic. Physicians report that unmet needs in XLRP management include more standardized assessment of quality of life; easier and earlier access to specialists, genetic testing, patient support programs, and effective treatment options.

show abstract

“…Panel testing was chosen as the first line of testing given the significant genetic heterogeneity of inherited retinal dystrophies and the significant phenotypic overlap between different genetic conditions leading to retinal dystrophy. 1 This panel identified a homozygous pathogenic variant in ALMS1 , c.2135_2136delCT (p.Ser712TyrfsTer6). The variant meets ACMG criteria for pathogenicity.…”

Section: Case Reportmentioning

confidence: 99%