Novel findings in a Swedish primary familial brain calcification cohort.

Autor: Sennfält S; Department of Neurology, Karolinska University Hospital, Hälsovägen 13 R52, 141 86 Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: stefan.sennfalt@gmail.com., Gustavsson P; Department of Clinical Genetics, Karolinska University Hospital, Karolinska Vägen, 171 76500 Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: peter.gustavsson@ki.se., Malmgren H; Department of Clinical Genetics, Karolinska University Hospital, Karolinska Vägen, 171 76500 Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: helena.malmgren@ki.se., Gilland E; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Blå stråket 7, 413 46 Göteborg, Sweden. Electronic address: ericgilland.jobb@telia.com., Almqvist H; Department of Clinical Neuroscience, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden; Department of Radiology, Capio S:t Goran Hospital, Sankt Göransplan 1, 112 19 Stockholm, Sweden. Electronic address: hakan.almqvist@capiostgoran.se., Oscarson M; Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Anna Steckséns g 47, 171 76 Solna, Sweden. Electronic address: mikael.oscarson@regionstockholm.se., Engvall M; Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Anna Steckséns g 47, 171 76 Solna, Sweden. Electronic address: martin.engvall@ki.se., Björkhem I; Science for Life Laboratory, Stockholm, Tomtebodavägen 23, 171 65 Solna, Sweden. Electronic address: ingemar.bjorkhem@ki.se., Nilsson D; Department of Clinical Genetics, Karolinska University Hospital, Karolinska Vägen, 171 76500 Solna, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Alfred Nobels Allé 8, 141 52 Huddinge, Sweden. Electronic address: daniel.nilsson@ki.se., Lagerstedt-Robinson K; Department of Clinical Genetics, Karolinska University Hospital, Karolinska Vägen, 171 76500 Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: kristina.lagerstedt@ki.se., Svenningsson P; Department of Neurology, Karolinska University Hospital, Hälsovägen 13 R52, 141 86 Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: per.svenningsson@ki.se., Paucar M; Department of Neurology, Karolinska University Hospital, Hälsovägen 13 R52, 141 86 Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden. Electronic address: martin.paucar-arce@regionstockolm.se.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2024 May 15; Vol. 460, pp. 123020. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1016/j.jns.2024.123020
Abstrakt: Introduction: Brain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial. This paper aims to characterize a Swedish PFBC cohort including 25 patients: 20 from seven families and five sporadic cases.
Methods: Longitudinal clinical assessment and CT imaging were conducted, abnormalities were assessed using the total calcification score (TCS). Genetic analyses, including a panel of six known PFBC genes, were performed in all index and sporadic cases. Additionally, three patients carrying a novel pathogenic copy number variant in SLC20A2 had their cerebrospinal fluid phosphate (CSF-Pi) levels measured.
Results: Among the 25 patients, the majority (76%) displayed varying symptoms during the initial assessment including motor (60%), psychiatric (40%), and/or cognitive abnormalities (24%). Clinical progression was observed in most patients (78.6%), but there was no significant difference in calcification between the first and second scans, with mean scores of 27.3 and 32.8, respectively. In three families and two sporadic cases, pathogenic genetic variants were identified, including a novel finding, in the SLC20A2 gene. In the three tested patients, the CSF-Pi levels were normal.
Conclusions: This report demonstrates the variable expressivity seen in PFBC and includes a novel pathogenic variant in the SLC20A2 gene. In four families and three sporadic cases, no pathogenic variants were found, suggesting that new PFBC genes remain to be discovered.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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