Novel variant in BRAT1 with the lethal neonatal rigidity and multifocal seizure syndrome

Novel Biallelic Variant in the BRAT1 Gene Caused Nonprogressive Cerebellar Ataxia Syndrome

“…According to Table 1 , the variant type rather than the variant domain is closely related to the phenotype severity. For example, homozygous variants R78P and p. V62E, both located on the apoptosis-related N-terminal CIDE (cell death-inducing DFF-45-like effector) ( Lugovskoy et al, 1999 ; Choi et al, 2017 ), caused typical RMFSL ( Li et al, 2021 ) and mild NPCA ( Lugovskoy et al, 1999 ), respectively. Complex mechanisms such as the mutation affecting one or more as unidentified activities of this protein ( Kurosaki and Maquat, 2016 ) or associated with BRAT1-related pathways might be involved.…”

“…Intron retaining can reduce gene expression at the post-transcriptional level and thereby impose an additional level of gene regulation, such as the degradation of mRNA transcripts via nonsense-mediated decay (NMD) and the regulation of nuclear mRNA export ( Low et al, 2015 ; Schmitz et al, 2017 ). Wild-type BRAT1 was diffusely expressed in the cytoplasm and the nucleus ( Li et al, 2021 ). As-retained intron transcripts accumulate in the nucleus ( Boutz et al, 2015 ), which might also reduce the amount of cytoplasmic BRAT1 available for the downstream events.…”

Compound heterozygous loss‐of‐function variants in BRAT1 cause lethal neonatal rigidity and multifocal seizure syndrome

“…Except for pneumonia, the clinical features of the proband in this study were comparable to typical characteristics of RMFSL. Although RMFSL has been reported in different populations, to our knowledge, RMFSL is less common among the Chinese population with only four cases reported to date (Burgess et al, 2019;Li et al, 2021;Qi et al, 2022;Van Ommeren et al, 2018). In 2018, Van et al described for the first time a female newborn affected by RMFSL with homozygous BRAT1 mutation variant c.1395G>C born to non-consanguineous Chinese parents (Van Ommeren et al, 2018).…”

“…Since the BRAT1 was first reported as the causative gene of RMFSL (Puffenberger et al, 2012), 45 mutations in the BRAT1 have been reported to date according to the Human Gene Mutation Database HGMD (http://www.hgmd.org/; Professional 2022.1) and the existing literature, including 20 missense/nonsense mutations, 8 splice mutations, 9 small deletions, 5 small insertions/duplications, and 3 gross deletions mutations (Figure 5, Table 1) (Capalbo et al, 2019; Colak et al, 2020; Fernández‐Jaén et al, 2016; Hanes et al, 2015; Heide et al, 2020; Li et al, 2021; Na et al, 2020; Qi et al, 2022; Scheffer et al, 2020; Szymańska et al, 2018; Wu et al, 2021). In this study, we found a sixth splice site mutation c.431‐2A>G (Colak et al, 2020; Horn et al, 2016; Srivastava et al, 2014; Stödberg et al, 2020; Rudolf et al, 2020).…”

A review of the clinical spectrum of BRAT1 disorders and case of developmental and epileptic encephalopathy surviving into adulthood

“… 14 months Balasundaram, 2021 [31] 1 Bilalelic deletion of at least exons 1–2 Day 1 Tonic-clonic, myoclonic RMFSL Corpus callosum thinning Bilateral medium–high voltage spikes over temporal and central regions, frequent multifocal seizures, background slowing, and no posterior rhythm. 2.5 months Li, 2021 [32] 1 Homozygous c.233G > C, p.(Arg78Pro) 1 month Myoclonic RMFSL Corpus callosum thinning Sharp wave discharges in the left forehead-parietal region than in the right forehead- parietal region. 7 months Stödberg, 2020 [18] 1 Compound heterozygous c.1771‐1G > C; p.?…”