Progranulin (GRN) mutations can result in a large variety of neurological phenotypes, which have not previously been identified by genetic testing based solely on inheritance patterns. Next generation sequencing can be used to detect infrequent occurrences, such as homozygosity in rare dominant diseases.
Why this matters
Mutations in GRN are linked to frontotemporal dementia (FTD). Heterozygous mutations are responsible for 20% of familial frontotemporal dementia; homozygous mutations lead to extensive neurological pathologies, and until now have only been identified in five patients from four families. Understanding better the diversity of characteristics of a homozygous mutation will enable improved understanding of the link to FTD, and better genetic counseling for affected families.