A novel granulin mutation in logopenic variant primary progressive aphasias: Case report and literature review

Abstract

Abstract Background Primary progressive aphasias (PPA) can be divided into 3 main variants, nonfluent/agrammatic, semantic, and logopenic variant. Logopenic variant PPA(lvPPA) was the third to be described clinically. Majority of these PPA patients harbored mutations in the granulin (GRN) gene on chromosome 17q21. Case presentation Based on the reported patient’s clinical and neuroimaging data, we considered a diagnosis of lvPPA, characterized by impaired single-word retrieval in spontaneous speech and naming, and impaired repetition of sentences and phrases, with relatively preserved single-word comprehension, object knowledge, motor speech, and no speech errors in spontaneous speech or naming. MRI of head revealed marked lateral atrophy in the left parietal cortex and a gradual change over a period of six years. A heterozygous 10-bp frameshift deletion (C.274_283del ATGCGGGGAT)was identified in exon 4 of the GRN gene (NM_002087.4), leading to alteration of cysteine to alanine at amino acid 92 and creation of a premature stop codon at position 161. This GRN associated lvPPA presentation is rarely previously reported. Conclusions We summarized clinical, MRI and genetic features of an lvPPA individual carried a novel GRN mutation. We have provided a clue for exploring the pathogenicity significance of GRN mutation in frontotemporal lobar degeneration(FTLD), which broadens the genetic and phenotypic spectrum of FTLD.