Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia

Hiromoto, Yoshitaka; Azuma, Yoshiteru; Suzuki, Yuichi; Hoshina, Megumi; Uchiyama, Yuri; Mitsuhashi, Satomi; Miyatake, Satoko; Mizuguchi, Takeshi; Takata, Atsushi; Miyake, Noriko; Kato, Mitsuhiro; Matsumoto, Naomichi

doi:10.1038/s41439-020-00131-9

Cited by 6 publications

(4 citation statements)

References 22 publications

(35 reference statements)

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“…PDZD2 also contributes to the functional expression of Nav1.8 ion channel, which is encoded by SCN10A , a QRV enriched gene in NAFE 52 Another gene with shorter distance to known epilepsy genes, FLNA , has itself been associated with epilepsy and seizure disorders 5 . FLNA is also known to interact with HCN1 channels during neuronal excitability modulation in the mature brain 53 . Additionally, FLNA also controls ECM remodeling by regulating metalloproteinase activity and hence ECM degradation 54 Based on the enrichment of ECM genes, we suggest that especially for NAFE, genetic variants which may impact ECM morphology could lead to imbalance in excitatory and inhibitory signals 55 and hence underlie epileptogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Another gene with shorter distance to known epilepsy genes, FLNA , has itself been associated with epilepsy and seizure disorders 5 . FLNA is also known to interact with HCN1 channels during neuronal excitability modulation in the mature brain 53 . Additionally, FLNA also controls ECM remodeling by regulating metalloproteinase activity and hence ECM degradation 54 .…”

Section: Discussionmentioning

confidence: 99%

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The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology

Bundalian

Chen

et al. 2023

Preprint

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Previous studies suggested that severe epilepsies e.g., developmental and epileptic encephalopathies (DEE) are mainly caused by ultra-rare de novo genetic variants. For milder phenotypes, rare genetic variants could contribute to the phenotype. To determine the importance of rare variants for different epilepsy types, we analyzed a whole-exome sequencing cohort of 9,170 epilepsy-affected individuals and 8,436 controls. Here, we separately analyzed three different groups of epilepsies: severe DEEs, genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We required qualifying rare variants (QRVs) to occur in controls at a minor allele frequency ≤ 1:1,000, to be predicted as deleterious (CADD≥20), and to have an odds ratio in epilepsy cases ≥2. We identified genes enriched with QRVs in DEE (n=21), NAFE (n=72), and GGE (n=32). Enrichment was strongest in NAFE and weakest in DEE. This suggests that rare variants may play a more important role for causality of NAFE than in DEE. Moreover, we found that QRV-carrying genes e.g., HSGP2, FLNA or TNC are involved in structuring the brain extracellular matrix. The present study confirms an involvement of rare variants for NAFE, while in DEE and GGE, the contribution of such variants appears more limited.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology

Bundalian

Chen

et al. 2023

Preprint

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“…Consequently, robust FLNa binding curtails integrin-dependent cell migration by impeding transient membrane protrusion and cell polarization [21]. Furthermore, loss-of-function mutations in FLNa are implicated in impaired neural cell migration in response to microenvironmental cues, along with the development of vascular system defects [22][23][24][25][26].…”

Section: Filamin a And Its Functionsmentioning

confidence: 99%

Role of Filamin A in Growth and Migration of Breast Cancer—Review

Zawadka,

Zielińska,

Gagat

et al. 2024

CIMB

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Despite ongoing research in the field of breast cancer, the morbidity rates indicate that the disease remains a significant challenge. While patients with primary tumors have relatively high survival rates, these chances significantly decrease once metastasis begins. Thus, exploring alternative approaches, such as targeting proteins overexpressed in malignancies, remains significant. Filamin A (FLNa), an actin-binding protein (ABP), is involved in various cellular processes, including cell migration, adhesion, proliferation, and DNA repair. Overexpression of the protein was confirmed in samples from patients with numerous oncological diseases such as prostate, lung, gastric, colorectal, and pancreatic cancer, as well as breast cancer. Although most researchers concur on its role in promoting breast cancer progression and aggressiveness, discrepancies exist among studies. Moreover, the precise mechanisms through which FLNa affects cell migration, invasion, and even cancer progression remain unclear, highlighting the need for further research. To evaluate FLNa’s potential as a therapeutic target, we have summarized its roles in breast cancer.

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“…FLNA is located in the q28 region of the X chromosome [ 1 , 2 ]. It encodes a widely expressed filamentous protein that acts on intracellular actin binding, and is involved in cell migration, mechano sensing, and cell signaling [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Periventricular nodular heterotopias is associated with mutation at the FLNA locus-a case history and a literature review

Yang

Yin

et al. 2023

BMC Pediatr

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Background Periventricular nodular heterotopia (PNH), associated with FLNA mutations, is a rare clinical condition potentially associated with multiple systemic conditions, including cardiac, pulmonary, skeletal, and cutaneous diseases. However, due to a paucity of information in the literature, accurate prognostic advice cannot be provided to patients with the disease. Case presentation We report a 2-year-old female whose PNH was associated with a nonsense mutation in the q28 region of the X chromosome, in exon 31 of FLNA (c.5159dupA). The patient is currently seizure-free and has no congenital heart disease, lung disease or skeletal or joint issues, and her development is normal. Conclusions FLNA-associated PNH is a genetically-heterogeneous disease, and the FLNA mutation, c.5159dupA (p.Tyr1720*) is a newly identified pathogenic variant. FLNA characterization will help the clinical diagnosis and treatment of PNH and provide individualized genetic counseling for patients.

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Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia

Cited by 6 publications

References 22 publications

The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology

The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology

Role of Filamin A in Growth and Migration of Breast Cancer—Review

Periventricular nodular heterotopias is associated with mutation at the FLNA locus-a case history and a literature review

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