Advantages and disadvantages of molecular testing in ophthalmology

Abstract

Genetic eye diseases (GEDs) are clinically and genetically heterogeneous. Results from molecular genetic testing are redefining the etiology and clinical spectrum of these heritable diseases, helping to explain the observed overlap in clinical phenotypes. Patients and parents benefit from DNA analysis when results confirm a diagnosis or make a diagnosis more specific. Accurate counseling can then be provided regarding the prognosis, presymptomatic diagnosis, life and family-planning issues and whether to anticipate other ocular or systemic medical problems. Patients hope that mutation identification will enable their participation in future clinical trials for treatment. Requests for molecular testing are increasing while those in the visually impaired world and the healthcare professionals who manage them wait to learn long-term results of the first human clinical trials for a GED to be treated with gene therapy, RPE65-type Leber congenital amaurosis. The advantages and disadvantages of molecular testing for ocular diseases are discussed in general, followed by specific details for over 40 GEDs. Some cases are presented to demonstrate testing issues.

Keywords::

• albinism
• aniridia
• gene therapy
• genetic counseling
• macular dystrophy
• molecular genetic testing
• ocular genetics
• retinal dystrophy
• retinitis pigmentosa
• retinoblastoma
• review

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

adRP: Autosomal dominant RP; CORD: Cone–rod dystrophies; ERG: Electroretinogram; HCP: Healthcare professional; OA: Ocular albinism; OCA: Oculocutaneous albinism; RB: Retinoblastoma; RP: Retinitis pigmentosa; VEP: Visual evoked potential.

adRP: Autosomal dominant RP; arRP: Autosomal recessive RP; BBS: Bardet–Biedl syndrome; CHS: Chediak–Higashi syndrome; CSNB: Congenital stationary night blindness; FEVR: Familial exudative vitreoretinopathy; HPS: Hermansky–Pudlak syndrome; LCA: Leber congenital amaurosis; LHON: Leber hereditary optic neuropathy; MELAS: Myopathy, encephalopathy, lactic acidosis and stroke-like episodes; NARP: Neuropathy, ataxia and RP; NCMD: North Carolina macular dystrophy; OA: Ocular albinism; OCA: Oculocutaneous albinism; OPA: Optic atrophy; PHPV: Persistent hyperplastic primary vitreous; RP: Retinitis pigmentosa; VMD: Vitelliform macular dystrophy; WAGR: Wilms tumor–aniridia–genital anomalies–retardation; XL: X-linked.