A novel mutation in MYORG leads to primary familial brain calcification and cerebral infarction

Fahr's disease linked to a novel mutation in MYORG variants manifesting as paroxysmal limb stiffness and dysarthria: Case report and literature review

“…We searched through PubMed until April 1, 2023 for relevant studies and scanned the reference lists in the identified articles. We reviewed all reported cases of PFBC with biallelic MYORG mutations and summarized all the mutation sites in Table 1 (Arkadir et al, 2019 ; Chelban et al, 2020 ; Chen, Lin, et al, 2020 ; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Fei et al, 2021 ; Ferreira & de Oliveira, 2019 ; Forouhideh et al, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Li et al, 2022 ; Liu et al, 2021 ; Malaquias et al, 2020 ; Peng et al, 2018 ; Ramos et al, 2019 ; Sadok et al, 2023 ; Saranza et al, 2020 ; Taglia et al, 2019 ; Tekin et al, 2021 ; Tsai et al, 2022 ; Yang et al, 2022 ; Yao et al, 2018 ; Zeng et al, 2021 ). Data for 62 families have been reported, 51% of the patients were men and 49% were women.…”

“…Similar to previous studies (Grangeon et al, 2019 ; Taglia et al, 2019 ; Zeng et al, 2021 ), we observed that dysarthria is a prominent feature and the most common manifestation in patients with MYORG ‐PFBC, as well as other motor signs, including ataxia, dystonia, dyskinesia, Parkinsonism, and akinetic hypertonic syndrome. Ischemic stroke was also reported in five cases, and none of them had risk factors for stroke (Gao et al, 2022 ; Grangeon et al, 2019 ; Li et al, 2022 ; Yang et al, 2022 ). Central neuropathic pain was also observed in a 43‐year‐old Chinese woman (Peng et al, 2018 ).…”

“…Pontine calcifications are highly specific to MYORG ‐PFBC and are relatively rare in patients with AD‐PFBC. Among the reported cases of PFBC with biallelic MYORG mutations, 45 cases showed brainstem calcification (Arkadir et al, 2019 ; Chelban et al, 2020 ; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Ferreira & de Oliveira., 2019 ; Forouhideh et al, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Liu et al, 2021 ; Ramos et al, 2019 ; Saranza et al, 2020 ; Taglia et al, 2019 ;Tsai et al, 2022 ; Zeng et al, 2021 ) and 24 cases showed pontine calcification (Arkadir et al, 2019 ; Chelban et al, 2020 ; Ferreira & de Oliveira, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Ramos et al, 2019 ; Taglia et al, 2019 ; Tsai et al, 2022 ; Zeng et al, 2021 ). However, the brainstem tropism of lesions associated with MYORG mutations remains unknown.…”

“…The novel frameshift mutation identified in our patient was located in the unknown function domain. To date, 24 mutations in this domain have been reported (Chelban et al, 2020 ; Chen, Lin, et al, 2020 ; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Ferreira & de Oliveira, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Li et al, 2022 ; Malaquias et al, 2020 ; Sadok et al, 2023 ; Taglia et al, 2019 ; Tekin et al, 2021 ; Yang et al, 2022 ; Yao et al, 2018 ; Zeng et al, 2021 ), suggesting that this region plays an important role in MYORG , leading to PFBC. Therefore, more studies are recommended to investigate the correlations between mutation sites, pathogenicity‐implicated imaging findings, and clinical phenotypes.…”

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

“…Mutations in MYORG may cause damage to the neurovascular unit, and accelerate the deposition of calcium and other minerals in small arteries, capillaries, small veins, and perivascular spaces; such neurovascular unit impairment could cause damage to the blood-brain barrier ( 8 , 17 ). MYORG mutations have also been reported in brain hypoperfusion and cerebral infarction ( 12 , 14 , 21 ). However, it has been mentioned in the vascular theory that intracranial vasoconstriction causes migraine aura symptoms, followed by intracranial and extracranial vasodilatation leading to pulsatile headache production.…”