A novel PDGFRB sequence variant in a family with a mild form of primary familial brain calcification: A case report and a review of the literature

Stine Westergaard Mathorne, Kristina Sørensen, Christina Fagerberg, Matthias Bode, Jens Michael Hertz*

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Resumé

Background: Primary familial brain calcification is a rare autosomal dominant or recessive neurodegenerative disease, characterized by bilateral brain calcifications in different areas of the brain. It is a clinically heterogeneous disease and patients are reported to exhibit a wide spectrum of neurological and psychiatric symptoms. Mutations in five genes have been identified so far including SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG. PDGFRB encodes the platelet-derived growth factor receptor-beta, and is expressed in neurons, vascular smooth muscle cells and pericytes. Patients with a PDGFRB mutation seem to exhibit a milder phenotype and milder brain calcification on brain imaging than patients with SLC20A2 and PDGFB mutations. However, this is based on a few observations so far. Case presentation: We present a Danish family with bilateral brain calcifications and mild clinical symptoms of primary familial brain calcification, segregating with a novel PDGFRB sequence variant: c.1834G > A; p.(Gly612Arg), detected by whole exome sequencing. The variant results in physiochemical changes at the amino acid level, and affects a highly conserved nucleotide as well as amino acid. It is located in the tyrosine kinase domain of PDGFRβ. Segregation analysis and in silico analyses predicted the missense variant to be disease causing. Conclusion: Our study confirms that PDGFRB mutation carriers in general have a mild clinical phenotype, and basal ganglia calcifications can be detected by a CT scan, also in asymptomatic mutation carriers.

OriginalsprogEngelsk
Artikelnummer60
TidsskriftBMC Neurology
Vol/bind19
Antal sider6
ISSN1471-2377
DOI
StatusUdgivet - 12. apr. 2019

Fingeraftryk

Platelet-Derived Growth Factor beta Receptor
Mutation
Proto-Oncogene Proteins c-sis
Exome
Amino Acids
Pericytes
Vascular Smooth Muscle
Neuroimaging
Neurodegenerative Diseases
Computer Simulation
Neurons

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title = "A novel PDGFRB sequence variant in a family with a mild form of primary familial brain calcification: A case report and a review of the literature",
abstract = "Background: Primary familial brain calcification is a rare autosomal dominant or recessive neurodegenerative disease, characterized by bilateral brain calcifications in different areas of the brain. It is a clinically heterogeneous disease and patients are reported to exhibit a wide spectrum of neurological and psychiatric symptoms. Mutations in five genes have been identified so far including SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG. PDGFRB encodes the platelet-derived growth factor receptor-beta, and is expressed in neurons, vascular smooth muscle cells and pericytes. Patients with a PDGFRB mutation seem to exhibit a milder phenotype and milder brain calcification on brain imaging than patients with SLC20A2 and PDGFB mutations. However, this is based on a few observations so far. Case presentation: We present a Danish family with bilateral brain calcifications and mild clinical symptoms of primary familial brain calcification, segregating with a novel PDGFRB sequence variant: c.1834G > A; p.(Gly612Arg), detected by whole exome sequencing. The variant results in physiochemical changes at the amino acid level, and affects a highly conserved nucleotide as well as amino acid. It is located in the tyrosine kinase domain of PDGFRβ. Segregation analysis and in silico analyses predicted the missense variant to be disease causing. Conclusion: Our study confirms that PDGFRB mutation carriers in general have a mild clinical phenotype, and basal ganglia calcifications can be detected by a CT scan, also in asymptomatic mutation carriers.",
keywords = "Fahr syndrome, PDGFRB, Primary familial brain calcification, Humans, Middle Aged, Male, Tomography, X-Ray Computed, Neurodegenerative Diseases/genetics, Brain Diseases/genetics, Receptor, Platelet-Derived Growth Factor beta/genetics, Pedigree, Denmark, Female, Heterozygote, Mutation, Calcinosis/genetics",
author = "Mathorne, {Stine Westergaard} and Kristina S{\o}rensen and Christina Fagerberg and Matthias Bode and Hertz, {Jens Michael}",
year = "2019",
month = "4",
day = "12",
doi = "10.1186/s12883-019-1292-8",
language = "English",
volume = "19",
journal = "B M C Neurology",
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publisher = "BioMed Central",

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TY - JOUR

T1 - A novel PDGFRB sequence variant in a family with a mild form of primary familial brain calcification

T2 - A case report and a review of the literature

AU - Mathorne, Stine Westergaard

AU - Sørensen, Kristina

AU - Fagerberg, Christina

AU - Bode, Matthias

AU - Hertz, Jens Michael

PY - 2019/4/12

Y1 - 2019/4/12

N2 - Background: Primary familial brain calcification is a rare autosomal dominant or recessive neurodegenerative disease, characterized by bilateral brain calcifications in different areas of the brain. It is a clinically heterogeneous disease and patients are reported to exhibit a wide spectrum of neurological and psychiatric symptoms. Mutations in five genes have been identified so far including SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG. PDGFRB encodes the platelet-derived growth factor receptor-beta, and is expressed in neurons, vascular smooth muscle cells and pericytes. Patients with a PDGFRB mutation seem to exhibit a milder phenotype and milder brain calcification on brain imaging than patients with SLC20A2 and PDGFB mutations. However, this is based on a few observations so far. Case presentation: We present a Danish family with bilateral brain calcifications and mild clinical symptoms of primary familial brain calcification, segregating with a novel PDGFRB sequence variant: c.1834G > A; p.(Gly612Arg), detected by whole exome sequencing. The variant results in physiochemical changes at the amino acid level, and affects a highly conserved nucleotide as well as amino acid. It is located in the tyrosine kinase domain of PDGFRβ. Segregation analysis and in silico analyses predicted the missense variant to be disease causing. Conclusion: Our study confirms that PDGFRB mutation carriers in general have a mild clinical phenotype, and basal ganglia calcifications can be detected by a CT scan, also in asymptomatic mutation carriers.

AB - Background: Primary familial brain calcification is a rare autosomal dominant or recessive neurodegenerative disease, characterized by bilateral brain calcifications in different areas of the brain. It is a clinically heterogeneous disease and patients are reported to exhibit a wide spectrum of neurological and psychiatric symptoms. Mutations in five genes have been identified so far including SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG. PDGFRB encodes the platelet-derived growth factor receptor-beta, and is expressed in neurons, vascular smooth muscle cells and pericytes. Patients with a PDGFRB mutation seem to exhibit a milder phenotype and milder brain calcification on brain imaging than patients with SLC20A2 and PDGFB mutations. However, this is based on a few observations so far. Case presentation: We present a Danish family with bilateral brain calcifications and mild clinical symptoms of primary familial brain calcification, segregating with a novel PDGFRB sequence variant: c.1834G > A; p.(Gly612Arg), detected by whole exome sequencing. The variant results in physiochemical changes at the amino acid level, and affects a highly conserved nucleotide as well as amino acid. It is located in the tyrosine kinase domain of PDGFRβ. Segregation analysis and in silico analyses predicted the missense variant to be disease causing. Conclusion: Our study confirms that PDGFRB mutation carriers in general have a mild clinical phenotype, and basal ganglia calcifications can be detected by a CT scan, also in asymptomatic mutation carriers.

KW - Fahr syndrome

KW - PDGFRB

KW - Primary familial brain calcification

KW - Humans

KW - Middle Aged

KW - Male

KW - Tomography, X-Ray Computed

KW - Neurodegenerative Diseases/genetics

KW - Brain Diseases/genetics

KW - Receptor, Platelet-Derived Growth Factor beta/genetics

KW - Pedigree

KW - Denmark

KW - Female

KW - Heterozygote

KW - Mutation

KW - Calcinosis/genetics

U2 - 10.1186/s12883-019-1292-8

DO - 10.1186/s12883-019-1292-8

M3 - Journal article

C2 - 30979360

AN - SCOPUS:85064350915

VL - 19

JO - B M C Neurology

JF - B M C Neurology

SN - 1471-2377

M1 - 60

ER -