To the Editor:Primary familial brain calcification (PFBC) is a rare genetically degenerative disease that is generally characterized by symmetrical,bilateral calcinosis in the basal ganglia,thalamus,dentate nuclei,and...To the Editor:Primary familial brain calcification (PFBC) is a rare genetically degenerative disease that is generally characterized by symmetrical,bilateral calcinosis in the basal ganglia,thalamus,dentate nuclei,and other brain regions and mainly manifests with neurological and psychiatric symptoms. A growing number of studies have reported associations between this condition and pathogenic mutations,such as those in the SLC2OA2,PDGFRB,PDGFB,XPR1,and MYORG genes, Few studies have evaluated familial clinical characteristics, such as the volume of basal ganglia calcification (VBGC), and the results of clinical tests to determine serum levels of calcium (Ca),magnesium (Mg),phosphorus (P),iron (Fe), aluminum (A1),arsenic (As),cobalt (Co),parathyroid hormone (PTH),and calcitonin (Ct),or the relationship between patient age and the VBGC in PFBC.展开更多
Considered rare tumors, gangliogliomas account for 0.4% - 0.9% of intracranial neoplasms. The peak of its incidence occurs between 10 and 20 years of age. These tumors are composed of glial and ganglion cells and they...Considered rare tumors, gangliogliomas account for 0.4% - 0.9% of intracranial neoplasms. The peak of its incidence occurs between 10 and 20 years of age. These tumors are composed of glial and ganglion cells and they are relatively low-grade neoplasms associated with good prognoses. We report a case of an atypical calcified ganglioglioma in an 18-year-old woman with history of four months of stabbing right-sided parietal headache, paroxysmal. On image studies were noted the presence of thick wall calcification in gangliogliomas. Although rare, this atypical ganglioglioma should be included in the differential diagnosis of lesions occurring in this area of the brain.展开更多
Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ata...Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and epilepsy.Currently,the etiology of PFBC is largely unknown,and no specific prevention or treatment is available.During the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in PFBC.In this review,considering mechanistic studies of these genes at the cellular level and in animals,we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients.Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.展开更多
PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD ...PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD domains are crucial for the Pi transport,but the role of PiT2-loop7 remains unclear.In PFBC patients,mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion.To date,six missense mutations have been identified in PiT2-loop7;however,the mechanisms by which these mutations cause PFBC are poorly understood.Here,we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2.Furthermore,we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase(AMPK)-or protein kinase B(AKT)-mediated PiT2 phosphorylation.In contrast,the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities.These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2.This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.展开更多
Background: Fahr’s disease, also recognized as Idiopathic Basal Ganglia Calcification (IBGC) or Primary Familial Brain Calcification (PFBC), was first identified by the German neurologist Karl Theodor Fahr in 1930. T...Background: Fahr’s disease, also recognized as Idiopathic Basal Ganglia Calcification (IBGC) or Primary Familial Brain Calcification (PFBC), was first identified by the German neurologist Karl Theodor Fahr in 1930. This rare condition, which involves the calcification of the basal ganglia and presents significant treatment challenges, is most commonly diagnosed in middle-aged adults and is notably uncommon in children. Purpose: We report a case of a younger patient and review this disease as an aid to early detection and diagnosis of the disease. Case Introduction: In this report, we present a unique case of Fahr’s disease in a child, where epilepsy manifested as the initial symptom during infancy. In this report, we present a case of Fahr’s disease in a child who presented with epilepsy as the first symptom in infancy. The child had no imaging abnormalities at the onset of the seizure, and subsequent antiepileptic drugs were reduced and discontinued, and when the seizure recurred 3 years later, a perfect cranial CT revealed symmetrical calcifications in the brain, which gradually worsened, and subsequently the child was unable to take care of himself and had regression of his psychomotor development, and the family requested discharge from the hospital, and then the child died during the follow-up visit. Conclusion: The disease is currently associated with a number of disorders for which there is no specific treatment, and half of all patients currently have a well-defined gene, emphasizing more importantly the importance of genetic counseling for parents known to be at risk prior to conception.展开更多
OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations...OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations.METHODS In order to apply the IBGC model in mice,we introduced S602 W point mutation into the mouse Slc20a2.Mice(3months old)with homozygous mutation developed brain calcification as similar as IBGC in human.The SYM decoction was diluted and added into the drinking water of 2-week-old homozygous Slc20a2 KI mice for 5months.Another group of homozygous Slc20a2 KI mice were set as control and received no treatment.After 5months,to analyze the effect of the SYM decoction on brain calcification,pathological sections with the brain of Slc20a2 KI mice were made and stained.RESULTS Calcified nodules were not seen in the brain of Slc20a2 KI mice that received SYM decoction treatment,while the control group developed multiple calcifications in the thalamus region.CONCLUSION SYM decoction produced preventive effect on the formation of calcified nodules in IBGC model mice,which might be useful for the treatment of IBGC caused by SLC20A2 mutations.展开更多
基金the grants from the Health and Family Planning Commission of Hunan Province (No.B2015-106)the Natural Science Foundation of Hunan Province of China (No.2018JJ6012).
文摘To the Editor:Primary familial brain calcification (PFBC) is a rare genetically degenerative disease that is generally characterized by symmetrical,bilateral calcinosis in the basal ganglia,thalamus,dentate nuclei,and other brain regions and mainly manifests with neurological and psychiatric symptoms. A growing number of studies have reported associations between this condition and pathogenic mutations,such as those in the SLC2OA2,PDGFRB,PDGFB,XPR1,and MYORG genes, Few studies have evaluated familial clinical characteristics, such as the volume of basal ganglia calcification (VBGC), and the results of clinical tests to determine serum levels of calcium (Ca),magnesium (Mg),phosphorus (P),iron (Fe), aluminum (A1),arsenic (As),cobalt (Co),parathyroid hormone (PTH),and calcitonin (Ct),or the relationship between patient age and the VBGC in PFBC.
文摘Considered rare tumors, gangliogliomas account for 0.4% - 0.9% of intracranial neoplasms. The peak of its incidence occurs between 10 and 20 years of age. These tumors are composed of glial and ganglion cells and they are relatively low-grade neoplasms associated with good prognoses. We report a case of an atypical calcified ganglioglioma in an 18-year-old woman with history of four months of stabbing right-sided parietal headache, paroxysmal. On image studies were noted the presence of thick wall calcification in gangliogliomas. Although rare, this atypical ganglioglioma should be included in the differential diagnosis of lesions occurring in this area of the brain.
基金supported by the National Natural Science Foundation of China(31871262)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Innovation Incentive Foundation(Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai,China).
文摘Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and epilepsy.Currently,the etiology of PFBC is largely unknown,and no specific prevention or treatment is available.During the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in PFBC.In this review,considering mechanistic studies of these genes at the cellular level and in animals,we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients.Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.
基金supported by the National Natural Science Foundation of China(31871262)a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05).
文摘PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD domains are crucial for the Pi transport,but the role of PiT2-loop7 remains unclear.In PFBC patients,mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion.To date,six missense mutations have been identified in PiT2-loop7;however,the mechanisms by which these mutations cause PFBC are poorly understood.Here,we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2.Furthermore,we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase(AMPK)-or protein kinase B(AKT)-mediated PiT2 phosphorylation.In contrast,the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities.These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2.This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
文摘Background: Fahr’s disease, also recognized as Idiopathic Basal Ganglia Calcification (IBGC) or Primary Familial Brain Calcification (PFBC), was first identified by the German neurologist Karl Theodor Fahr in 1930. This rare condition, which involves the calcification of the basal ganglia and presents significant treatment challenges, is most commonly diagnosed in middle-aged adults and is notably uncommon in children. Purpose: We report a case of a younger patient and review this disease as an aid to early detection and diagnosis of the disease. Case Introduction: In this report, we present a unique case of Fahr’s disease in a child, where epilepsy manifested as the initial symptom during infancy. In this report, we present a case of Fahr’s disease in a child who presented with epilepsy as the first symptom in infancy. The child had no imaging abnormalities at the onset of the seizure, and subsequent antiepileptic drugs were reduced and discontinued, and when the seizure recurred 3 years later, a perfect cranial CT revealed symmetrical calcifications in the brain, which gradually worsened, and subsequently the child was unable to take care of himself and had regression of his psychomotor development, and the family requested discharge from the hospital, and then the child died during the follow-up visit. Conclusion: The disease is currently associated with a number of disorders for which there is no specific treatment, and half of all patients currently have a well-defined gene, emphasizing more importantly the importance of genetic counseling for parents known to be at risk prior to conception.
基金The project supported by National Natural Science Foundation of China grants(31230045and 81271252)the National Science&Technology Pillar Program duringthe 12th Five-year Plan Period(2012BAI09B04)
文摘OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations.METHODS In order to apply the IBGC model in mice,we introduced S602 W point mutation into the mouse Slc20a2.Mice(3months old)with homozygous mutation developed brain calcification as similar as IBGC in human.The SYM decoction was diluted and added into the drinking water of 2-week-old homozygous Slc20a2 KI mice for 5months.Another group of homozygous Slc20a2 KI mice were set as control and received no treatment.After 5months,to analyze the effect of the SYM decoction on brain calcification,pathological sections with the brain of Slc20a2 KI mice were made and stained.RESULTS Calcified nodules were not seen in the brain of Slc20a2 KI mice that received SYM decoction treatment,while the control group developed multiple calcifications in the thalamus region.CONCLUSION SYM decoction produced preventive effect on the formation of calcified nodules in IBGC model mice,which might be useful for the treatment of IBGC caused by SLC20A2 mutations.
