Clinical Manifestations.

Abstract

Mutations in the progranulin gene on chromosome 17(GRN) is considered as one of most common causes of frontotemporal lobe degeneration. However, the phenotype and genotype correlation of GRN varies among different cohorts and ethnicities. In Chinese people, the genotype of GRN has not been fully elucidated. 1945 patients with dementia at Peking Union Medical College Hospital underwent next-generation sequencing (NGS) analysis. GRN variations classified as likely pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected. The clinical, neuropsychological and neuroimaging characters were investigated. Three patients with four likely pathogenic mutation: p.P50fs & p.W49_P50delinsX, p.P439fs, p.R110X, and thirteen patients with uncertain significance mutations were enrolled. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Asymmetrical atrophy of the frontal lobe and temporal lobe appeared in 64% GRN mutation carriers. Parietal lobe dysfunction or parietal lobe atrophy existed in all patients. White matter lesions existed in 79% patients. The majority of clinical phenotype was frontotemporal lobe degeneration, though cerebral vascular lesions were obvious in some of them especially among old onset patients. The proportion of ApoE e4 carriers were higher in old onset patients than those in young onset ones. GRN mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps.