title: Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation.
abstract: We and others have reported heterozygous progranulin mutations as an important cause of frontotemporal lobar degeneration (FTLD). It has been identified a complete progranulin deficiency because of a homozygous mutation in a sibling pair with neuronal ceroid lipofuscinosis (NCL). Here, we describe the first case of NCL caused by a homozygous progranulin mutation segregating in a family with neuropathological confirmed FTLD. In this FTLD-NCL family, we detail the clinical phenotype, neuropsychological evaluation and imaging data of our proband harboring a homozygous mutation, c.900_901dupGT, with serum progranulin level (<6 ng/mL). Symptoms included rapidly progressive visual deficit, slightly dysarthria, and cerebellar ataxia. The electroretinogram confirmed a severe attenuation of rod and cone responses compatible with retinal dystrophy diagnosis and magnetic resonance imaging showed severe global cerebellar atrophy. In contrast, heterozygous relatives presented behavioral variant of frontotemporal dementia (FTD) and some also developed extrapyramidal features compatible with corticobasal syndrome. Our findings suggest the importance of assessing serum progranulin levels in suspected recessive adult-onset NCL cases. Overall, a more holistic neurologic intervention is needed to guarantee a proper genetic counseling in cases like the present family where two distinct phenotypes are generated according to the individuals' mutation state.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, Neurogenetics Department, University of Coimbra, Coimbra, Portugal. Electronic address: mralmeida2008@gmail.com.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: Neurology Department, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Macário
authors.affiliation: Genetics Department, Pediatric Hospital of Coimbra, Coimbra, Portugal.
authors.forename: Lina
authors.initials: L
authors.lastname: Ramos
authors.affiliation: Neurology Department, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Baldeiras
authors.affiliation: Neurology Department, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Ribeiro
authors.affiliation: Neurology Department, Coimbra University Hospital, Coimbra, Portugal; Neurology Department, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
mesh_terms: D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D056726:Genetic Association Studies; D006579:Heterozygote; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D011174:Portugal; D000077153:Progranulins
chemical_list: D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: FTLD-NCL family; Frontotemporal lobar degeneration; Homozygous or heterozygous state; Neuronal ceroid lipofuscinosis; Progranulin mutation