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

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

doi:10.1186/s12883-019-1292-8

Cited by 9 publications

(8 citation statements)

References 31 publications

(47 reference statements)

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“…S1). Considering that four other family members of the oldest paraclinically unaffected individual do have brain calcification, 26 this woman may be the first case of reduced penetrance of the paraclinical phenotype in PFBC.…”

Section: Discussionmentioning

confidence: 90%

Genotype–Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review

et al. 2021

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A BS TRACT: This systematic MDSGene review covers individuals with confirmed genetic forms of primary familial brain calcification (PFBC) available in the literature. Data on 516 (47% men) individuals, carrying heterozygous variants in SLC20A2 (solute carrier family 20 member 2, 61%), PDGFB (platelet-derived growth factor subunit B, 12%), XPR1 (xenotropic and polytropic retrovirus receptor, 16%), or PDGFRB (platelet-derived growth factor receptor beta, 5%) or biallelic variants in MYORG (myogenesis-regulating glycosidase, 13%) or JAM2 (junctional adhesion molecule 2, 2%), were extracted from 93 articles. Nearly one-third of the mutation carriers were clinically unaffected. Carriers of PDGFRB variants were more likely to be clinically unaffected (54%), and the penetrance of SLC20A2 and XPR1 variants (<70%) was lower in comparison to the remaining three genes (>85%). Among the 349 clinically affected patients, 27% showed only motor and 31% only nonmotor symptoms/signs, whereas the remaining 42% had a combination thereof. While parkinsonism and speech disturbance were the most frequently reported motor manifestations, cognitive deficits, headache, and depression were the major nonmotor symptoms/signs. The basal ganglia were always calcified, and the cerebellum, thalamus, and white matter contained calcifications in 58%, 53%, and 43%, respectively, of individuals. In autosomaldominant PFBC, mutation severity influenced the number of calcified brain areas, which in turn correlated with the clinical status, whereby the risk of developing symptoms/signs more than doubled for each additional region with calcifications. Our systematic analysis provides the most comprehensive insight into genetic, clinical, and neuroimaging features of known PFBC forms, to date. In addition, it puts forth the penetrance estimates and newly discovered genotypephenotype relations that will improve counseling of individuals with mutations in PFBC genes.

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Section: Discussionmentioning

confidence: 90%

Genotype–Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review

et al. 2021

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“…XPR1 gene mutations were present in 6 cases (4.3%) [54]. Over the years, several case reports described mutation variants, with peculiar clinical presentation, in SLC20A2 [55–58], PDGFB [59, 60], PDGFRB [61, 62], and XPR1 [63, 64].…”

Section: Classificationmentioning

confidence: 99%

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

et al. 2019

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Basal ganglia calcifications could be incidental findings up to 20% of asymptomatic patients undergoing CT or MRI scan. The presence of neuropsychiatric symptoms associated with bilateral basal ganglia calcifications (which could occur in other peculiar brain structures, such as dentate nuclei) identifies a clinical picture defined as Fahr's Disease. This denomination mainly refers to idiopathic forms in which no metabolic or other underlying causes are identified. Recently, mutations in four different genes (SLC20A2, PDGFRB, PDGFB, and XPR1) were identified, together with novel mutations in the Myogenic Regulating Glycosylase gene, causing the occurrence of movement disorders, cognitive decline, and psychiatric symptoms. On the other hand, secondary forms, also identified as Fahr's syndrome, have been associated with different conditions: endocrine abnormalities of PTH, such as hypoparathyroidism, other genetically determined conditions, brain infections, or toxic exposure. The underlying pathophysiology seems to be related to an abnormal calcium/phosphorus homeostasis and transportation and alteration of the blood-brain barrier.

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“…Another case report described two adolescent sisters from an LMS family who presented with undetectable ovaries and hypoplastic uterine tissue, mammary glands, and nipples, which led to infertility [56]. In contrast to classically diagnosed LMS patients with limb defects, these two sisters developed normal hands and feet.…”

Section: Tp63 Mutants In Syndromic Infertilitymentioning

confidence: 99%

The Role of Mutant p63 in Female Fertility

Luan

et al. 2021

IJMS

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The transcription factor p63, one of the p53 family members, plays an essential role in regulating maternal reproduction and genomic integrity as well as epidermal development. TP63 (human)/Trp63 (mouse) produces multiple isoforms: TAp63 and ΔNp63, which possess a different N-terminus depending on two different promoters, and p63a, p63b, p63g, p63δ, and p63ε as products of alternative splicing at the C-terminus. TAp63 expression turns on in the nuclei of primordial germ cells in females and is maintained mainly in the oocyte nuclei of immature follicles. It has been established that TAp63 is the genomic guardian in oocytes of the female ovaries and plays a central role in determining the oocyte fate upon oocyte damage. Lately, there is increasing evidence that TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. Here, we review the biological functions of p63 in females and discuss the consequences of p63 mutations, which result in infertility in human patients.

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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

Cited by 9 publications

References 31 publications

Genotype–Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review

Genotype–Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review

Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features

The Role of Mutant p63 in Female Fertility

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