Sex influences clinical phenotype in valosin-containing protein mutations: A case family report and systematic literature review.

Autor: Leccese D; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Rodolico GR; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Sperti M; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Cassandrini D; Department of Molecular Medicine, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy., Bartolini M; Department of Radiology, AOU Careggi, 50139 Florence, Italy., Ingannato A; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Nacmias B; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, 50143 Florence, Italy., Bracco L; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Malandrini A; Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy., Santorelli FM; Department of Molecular Medicine, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy., Bessi V; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy., Matà S; Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy. Electronic address: masa@unifi.it.
Jazyk: angličtina
Zdroj: Clinical neurology and neurosurgery [Clin Neurol Neurosurg] 2023 Sep; Vol. 232, pp. 107875. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1016/j.clineuro.2023.107875
Abstrakt: Objective: Mutations in the valosin-containing protein (VCP) gene cause autosomal dominant multisystem proteinopathy 1 (MSP1), characterized by a variable combination of inclusion body myopathy (IBM), Paget's disease of bone (PDB), and frontotemporal dementia (FTD). Here we report a novel VCP missense mutations in an Italian family with FTD as the prevalent manifestation and compare our results with those described in the literature.
Methods: We described the clinical, molecular, and imaging data of the studied family. We also conducted a systematic literature search with the aim of comparing our findings with previously reported VCP-related phenotypes.
Results: A novel heterozygous VCP missense mutation (c 0.473 T > C/p.Met158Thr) was found in all the affected family members. The proband is a 69-year-old man affected by progressive muscle weakness since the age of 49. Muscle MRI showed patchy fatty infiltration in most muscles, and STIR sequences revealed an unusual signal increase in distal leg muscles. At age 65, he presented a cognitive disorder suggestive of behavioral variant FTD. A bone scintigraphy also revealed PDB. The patient's mother, his maternal aunt and her daughter had died following a history of cognitive deterioration consistent with FTD; the mother also had PDB. No relatives had any muscular impairments. Reviewing the literature data, we observed a different sex distribution of VCP-related phenotypes, being FTD prevalence higher among women as compared to men (51.2 % vs 31.2 %) and IBM prevalence higher among men as compared to women (92.1 % vs 72.8 %).
Discussion: This study broadened our clinical, genetic, and imaging knowledge of VCP-related disorders.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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