PARADIGM study, funded by the PNRR research grant, will focus on Eye Diseases (ED) and Neuro-Muscular Diseases (NMD) as groups of genetically heterogeneous diseases which are extensively studied by the Partners partecipating in the project; indeed ED and NMD are well clinically and molecularly characterized and approachable by drug-testing options already assessed and implemented by PARADIGM partners. ED and NMD represent good and compatible disease models as: * both are genetically heterogeneous disorders where missing heritability is likely to be hidden in non-coding variants; * many of the individual genes accountable for the ED and NMD cause autosomal recessive forms, increasing the chance of finding regulatory/splicing variants
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Inclusion Criteria: * patients/relatives of patients with clinical diagnosis of NMD/ED; * patients/relatives of patients with inconclusive ES and aCGH data (no pathogenic/likely pathogenic variant) or finding of only a single hit (a pathogenic or likely pathogenic variant) in an autosomal recessive gene by ES (or aCGH) or no pathogenic or likely pathogenic variant but detection of a large region of genomic homozygosity surrounding a candidate gene; * patients/relatives of patients with a finding of cryptic VUS (splicing/regulatory/noncoding CNVs) in ED/NMD genes or pathogenic cryptic variants in a selected number of representative cases. * Signed informed consent to participate in the study. Exclusion Criteria: \- Trios or nuclear families where both unaffected parents do not consent to participate will be excluded (similarly, a minimum number of 3 affected family members will be needed in multigenerational pedigrees).