Table 1 Summary of the key consensus recommendations regarding anamnesis and genetic testing

Anamnesis

When assessing a patient with suspected RPE65 mutation-associated inherited retinal disease, the anamnesis (medical history) must include:

 General ophthalmologic history

 Symptoms at onset

 Age at symptom onset

 Pedigree

 Inquiry about consanguinity

 Existence of other affected family members

 Signs of disease progression

 Previous/current therapy for ocular diseases

 Other previous visits to a general ophthalmologist or to a retina specialist

 Previous clinical assessment for vision (MRI, OCT, ERG, FAF)

 Presence or not of neurological or extra-ocular symptoms

 General pharmacologic history and ongoing medical treatments

 History of infectious diseases

 Other diseases

 Patient expectations

 Professional activities and lifestyle (for adult patients)

Genetic testing

Genetic testing for diagnosis must be carried out by certified laboratories

The certification of a genetic diagnostic laboratory is defined by the following criteria

 ISO certification

 Analysis of > 100 cases per year for genetic diagnosis and document a highly significant number of confirmed genetic diagnosis cases

 Being part of a network with medical geneticists and inherited retinal diseases specialists from other national and international centres

The certified laboratories conducting genetic testing for inherited retinal disease diagnosis must

 Have qualified geneticists with consolidated expertise in the genetics of hereditary retinal dystrophies

 Have standardised internal molecular analysis protocols

 Perform genetic counselling before and after testing

 Be part of a national diagnostic laboratories network and/or Genetic Scientific Society (e.g., SIGU)

 Rely on a complete multidisciplinary team (geneticists, retina specialist, molecular biologists, technicians, bioinformatician, genetic counsellor) already familiar with IRDs molecular diagnosis

 Be able to perform MLPA analysis

 Be able to perform both Sanger and multi-gene NGS tests

 Be able to perform in silico analysis

 Be able to perform in vitro protein functional assessment

 Participate in inherited retinal disease national/international registries

A qualified geneticist is defined as a geneticist with

 Consolidated expertise in the genetics of hereditary retinal dystrophies

 Updated knowledge of the state-of-the-art and proven track record in the field of genetics of IRDs

 Relevant published literature in the field

 Proactive interactions and collaborations with international counterparts as part of multicentre consortia

Active networking with national and international counterparts is particularly important for a qualified geneticist

 In the case of rare diseases with high genetic heterogeneity like RPE65-associated Inherited retinal disease

 To exchange knowledge and expertise with other geneticists and IRD specialists