Severe brain calcification and migraine headache caused by <i>SLC20A2</i> and <i>PDGFRB</i> heterozygous mutations in a five‐year‐old Chinese girl

Sun, Hao; Cao, Zhijian; Gao, Ruixi; Li, Yulei; Chen, Rui; Du, Shiyue; Ma, Ting; Wang, Junhan; Xu, Xuan; Liu, Jingyu

doi:10.1002/mgg3.1670

Cited by 7 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with our results, with variants in NAA60 affecting SLC20A2 PM localization and cellular P i homeostasis. Moreover, a complex PFBC genotype-phenotype spectrum emerges as cases that involve dose-dependent variants have been associated with a severe clinical and neuroimaging spectrum 32 . SLC20A2 heterozygous mutations are associated with the adult-onset phenotype, while homozygous SLC20A2 variants resulted in severe phenotype including growth retardation, microcephaly, and convulsion 33 , similar to some of the NAA60 variants reported here.…”

Section: Discussionmentioning

confidence: 99%

Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Chelban,

Aksnes,

Maroofian

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

show abstract

Section: Discussionmentioning

confidence: 99%

Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Chelban,

Aksnes,

Maroofian

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

“…The first type of mutation is located in extracellular Ig-like domains (D1–D5), causing the receptor to lose its ability to bind to PDGF-BB, such as R106P (D1), P154S (D2), R226C (D3) ( Sun et al, 2021 ; Lenglez et al, 2022 ), and R334Q (D4). The R334 is highly evolutionarily conserved in mammalian species.…”

Section: Discussionmentioning

confidence: 99%

Case report: Primary familial brain calcification associated with a rare PDGFRB variant, coexisting with nontraumatic osteonecrosis of the femoral head

Cao,

Luo,

Wang

2024

Front. Neurosci.

View full text Add to dashboard Cite

Primary familial brain calcification (PFBC) is a rare genetic neurodegenerative disorder characterized by bilateral calcifications in the brain. PFBC may manifest with a broad spectrum of motor, cognitive, and neuropsychiatric symptoms. Several causal genes have been identified in PFBC, which are inherited as both autosomal dominant and autosomal recessive traits. Herein, we present the case of a Chinese family diagnosed with PFBC. The family members carry a rare heterozygous variant (p. R334Q) in exon 7 of platelet-derived growth factor receptor β (PDGFRB) gene. The platelet-derived growth factor-B/PDGF receptor β (PDGF-B/PDGFRβ) signaling pathway plays a crucial role in pericyte development in various organs and tissues. Notably, this variant uniquely coexists with nontraumatic osteonecrosis of the femoral head. Additionally, we reviewed previous studies on PFBC-causing variants in PDGFRB.

show abstract

“…By analyzing this information, we found that patients with dysphagia, verbal impairment, cognitive impairment, and dyskinesia as primary symptoms were mainly middle-aged and elderly ( 14 – 18 ). Conversely, patients with headache as the main clinical symptom are generally younger ( 10 , 19 ). Therefore, we hypothesize that earlier age of onset is associated with increased risk of headache and migraine, and that other corresponding symptoms may then develop with age.…”

Section: Discussionmentioning

confidence: 99%

A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review

Song

Zhao

Wen³

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

Primary familial brain calcification (PFBC) is a disorder in which pathologic calcification of the basal ganglia, cerebellum, or other brain regions with bilateral symmetry occurs. Common clinical symptoms include dysarthria, cerebellar symptoms, motor deficits, and cognitive impairment. Genetic factors are an important cause of the disease; however autosomal recessive (AR) inheritance is rare. In 2018, the myogenesis-regulated glycosidase (MYORG) gene was the first to be associated with AR-PFBC. The present case is a 24-year-old woman with AR-PFBC that presented with migraine at the age of 16 years. Symmetrical patchy calcifications were seen in the bilateral cerebellopontine nuclei, thalamus, basal ganglia, and radiocoronal area on computed tomography and magnetic resonance imaging. AR-PFBC with migraine as the main clinical symptom is rare. Whole-exome sequencing revealed a compound heterozygous mutation in the MYORG gene, one of which has not been previously reported. Our case highlights the pathogenic profile of the MYORG gene, and demonstrates the need for exclusion of calcium deposits in the brain for migraine patients with AR inheritance.

show abstract

Severe brain calcification and migraine headache caused by SLC20A2 and PDGFRB heterozygous mutations in a five‐year‐old Chinese girl

Cited by 7 publications

References 17 publications

Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Case report: Primary familial brain calcification associated with a rare PDGFRB variant, coexisting with nontraumatic osteonecrosis of the femoral head

A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review

Contact Info

Product

Resources

About