Address methodological differences | Repeat-primed PCR should be combined with Southern blot for estimation of repeat size and not be used in isolation. Sequencing should be used for smaller repeat sizes. |
Deciphering role of DNA composition in expanded repeats | The ‘critical repeat size’ may not be key, but rather the exact composition within the expanded repeats, including the possibility of repeat interruptions. |
Developing novel genotyping methods | Developing the ability to conduct a fast comprehensive systematic screen for repeat expansions on a genome-wide level. |
Adopting a multigeneration intrafamilial approach | Phenotype–genotype correlations within large multigeneration families can minimise the effect of heterogeneity in genetic background and confounders. |
Detailed clinical phenotyping | Detailed clinical and neuropsychological profiling in symptomatic and asymptomatic carriers and healthy controls for accurate genotype–phenotype correlations. |
Developing better cellular models of C9orf72 | Patient-derived induced pluripotent stem cell neurons harbouring different repeat sizes and transgenic non-human primates can provide additional insights. |
Longitudinal cohort study | A longitudinal cohort including subjects with intermediate alleles with long-term follow-up supported by detailed clinical, neuroimaging and biochemical evaluation. |
Multicentre study approach for optimising sample size | A global multicentre approach with standardised protocols and a centralised genotyping laboratory will aid in identifying rare associations, elucidate variation according to ethnicity and minimise diagnostic errors. |