De novo heterozygous missense variants inATP11Aare associated with refractory focal epilepsy DOI

Zi-Long Ye,

Nan-Xiang Shen,

Xiang-Yun Luo

и другие.

Journal of Medical Genetics, Год журнала: 2025, Номер unknown, С. jmg - 110540

Опубликована: Апрель 4, 2025

Background ATP11A encodes an integral-membrane type IV P-type-adenosine triphosphatase that plays important role in neural development by maintaining membrane lipid asymmetry. de novo heterozygous missense variants have been reported to be associated with hypomyelinating leukodystrophy; however, the neurological symptoms of patients are often varying. In this study, we aimed explore relationship between and epilepsy. Methods Trio-based whole-exome sequencing was performed on focal Multiple bioinformatics analyses were used predict pathogenicity variants. Previously literature collected analyse relation phenotypes. Results Two identified two unrelated refractory epilepsy predicted pathogenic using multiple analyses. Then, six collected. Half (3/6) located on/near transmembrane regions (TMs) had more severe symptoms, while other half non-TM mild single indicating a correlation variant location phenotype. All showed progressively worsening conditions, potentially due gradually increased expression human brain over time. Conclusion This study suggested Missense variant-associated phenotypes range from epileptic seizures symptoms. It should noted potential.

Язык: Английский

Genetic and expressional insights into the association of TRAPPC10 variants with neurodevelopmental disorders DOI
Pengyu Wang, Wenhui Liu,

Yujie Gu

и другие.

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
De Novo ACTB Variant Associated With Juvenile‐Onset Temporal Lobe Epilepsy With Favorable Outcomes DOI Creative Commons

Hong-Jun Yan,

Peng-Yu Wang,

Wenhui Liu

и другие.

Human Mutation, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Genetic factors are estimated to contribute 80% of people with epilepsy. However, only four genes were reported be associated temporal lobe epilepsy (TLE). This study is aimed at investigating the association between ACTB and TLE. Trio‐based exome sequencing was performed in a patient, de novo variant identified. The patient presented TLE featuring by age onset juvenile, seizure‐free status adulthood, complications memory decline irritability, epileptic discharges bilateral lobes, hippocampal sclerosis. pathogenicity identified supposed multiple pieces evidence, including missense tolerance ratio 0%, high conservation affected residue, predicted “damaging” or “conserved” 17 silico tools, classification likely pathogenic American College Medical Genetics Genomics (ACMG) guidelines. Protein modeling indicated alteration protein structure stability caused variant. spatiotemporal expression consistent phenotypic features this patient. suggested that novel candidate causative gene correlation phenotypes spatial–temporal provides perspective for further exploration pathogenesis prognosis disease.

Язык: Английский

Процитировано

1
MDN1 variants cause susceptibility to epilepsy DOI Creative Commons

Q. G. Wen,

Dongming Zhang, Yan Ding

и другие.

Acta Epileptologica, Год журнала: 2025, Номер 7(1)

Опубликована: Март 3, 2025

Abstract Background The Midasin AAA (ATPase associated with various activities) ATPase 1 ( MDN1 ) gene, a member of the protein family, plays crucial role in ribosome maturation. is expressed human brain throughout life, especially during early development and adulthood. However, variants have not been previously reported patients epilepsy. This study aims to explore association between Methods Trios-based whole-exome sequencing was performed cohort epilepsy susceptibility from China Epilepsy Gene 1.0 Project. excess, damaging effects, molecular subregional implications variants, as well spatio-temporal expression , were analyzed validate gene-disease association. Results Compound heterozygous identified five unrelated febrile seizures or secondary Three presented seizures/epilepsy plus, while two developed damage (five seven years after). These either absent present at low frequencies control group, exhibited statistically significant higher case group compared controls. All missense predicted be by least one silico tool. In each pair compound allele located AAA2-AAA3 domains, other linker domain its vicinity. contrast, most asymptomatic outside suggesting implication variants. Conclusions potentially gene for

Язык: Английский

Процитировано

1
RYR3 Variants Are Potentially Associated With Idiopathic (Non‐Lesional) Partial Epilepsy/Susceptibility of Seizures, Toward Understanding the Gene‐Disease Association by Genetic Dependent Nature DOI Open Access

Yang Tian,

Yunqi Hou,

Qiong‐Xiang Zhai

и другие.

American Journal of Medical Genetics Part B Neuropsychiatric Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

The RYR3 gene encodes a brain-type ryanodine receptor that functions to release calcium from intracellular storage and plays an essential role in signaling. associations between variants brain disorders remain unknown. We performed whole-exome sequencing patients with idiopathic (non-lesional) partial epilepsy of unknown etiology. One de novo missense six biallelic were identified seven unrelated cases. These had no or extremely low allele frequencies the general population predicted alter hydrogen bonds/decrease protein stability. Patients presented seizures secondarily generalized tonic-clonic seizures. All seizure-free with/without anti-seizure treatment. Four showed antecedent febrile seizures, typical susceptibility disorder is related precipitating factor fever. genetic dependence nature (GDN) RYR3, which defined as distinct impact absence on normal life, "obligatory" (causing disease phenotypes). Complete abolishing results abnormal phenotypes instead lethality, whereas partial/mild impairment (usually more common) associated mild increased disease, consistent our findings. therefore potentially candidate for epilepsy.

Язык: Английский

Процитировано

0
The novel role of foxi3 in zebrafish mandibular development DOI Creative Commons
Xin Chen, Run Yang, Tianyu Zhang

и другие.

Cells and Development, Год журнала: 2025, Номер unknown, С. 204016 - 204016

Опубликована: Фев. 1, 2025

Recent studies have identified pathogenic variants in the FOXI3 gene associated with craniofacial microsomia pedigrees. In zebrafish, foxi1 is considered a functional homolog of mouse Foxi3. However, research on foxi3a and foxi3b, which display homologous genes naming has predominantly focused their roles epidermal ionocyte function. Our study reveals that disruption or foxi3b results reduced number cranial neural crest cells (CNCCs) hypoplastic mandibular cartilage zebrafish. These findings introduce new perspective homologs highlight an unrecognized role foxi3 zebrafish CNCC development.

Язык: Английский

Процитировано

0
Biallelic SCN1A variants with divergent epilepsy phenotypes DOI Creative Commons
Rebecca D. Pentz, Rebecca F. Hough, Chumei Li

и другие.

Seizure, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Pathogenic SCN1A variants most commonly cause autosomal dominant Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+). However, rare homozygous have also been reported. We report two new cases of associated divergent phenotypes. retrospectively reviewed the charts unrelated patients different variants. all published biallelic pathogenic variants, focusing on Patient 1 had a c. 1676T>A, (p. Ile559Asn) variant uncertain significance, inherited from asymptomatic parents. exhibited early afebrile controlled by first-line anti-seizure medications no or status epilepticus, as well profound developmental delay, macrocephaly, mild dysmorphic features. 2 4970G>A, Arg1657His) carried This patient presented early, recurrent, prolonged seizures, moderate motor dysfunction was diagnosed syndrome. identified 16 further literature. Including our cases, 9/18 (50 %) were 6/18 (33 GEFS+. The mean age seizure onset 7 months (range 3-19 months). Phenotypes ranged intact neurodevelopment to delay refractory epilepsy. These highlight expand phenotypic spectrum While some present typically for Dravet/GEFS+, others may in absence epilepticus. Further studies are needed confirm genotype-phenotype relationships.

Язык: Английский

Процитировано

0
De novo TANC2 variants caused developmental and epileptic encephalopathy and epilepsy DOI Open Access
Sheng Luo, Wenjun Zhang,

Mi Jiang

и другие.

Epilepsia, Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

Abstract Objective The TANC2 gene encodes a scaffolding synaptic protein with essential roles in transmission. This study aims to explore the association between and epilepsy mechanism underlying phenotypic variation. Methods Trio‐based exome sequencing was performed patients from China Epilepsy 1.0 cohort. validated Drosophila model. role of development investigated by single‐cell RNA cerebral organoids spatiotemporal expression across brain regions. Results De novo variants were identified six unrelated cases, including four null two missense variants. classified as “pathogenic”/“likely pathogenic,” according American College Medical Genetics Genomics guidelines. Patients exhibited severe phenotypes, three neurodevelopmental disorders (NDDs) one developmental epileptic encephalopathy (DEE). In contrast, presented only epilepsy. Genotype–phenotype correlation analysis revealed that associated NDD mostly variants, whereas or NDD‐associated more damage effects, compared epilepsy‐associated Functional studies suggested knockdown led increased susceptibility seizure‐like behavior. expresses highly brain, peaks early fetal, infancy, adulthood, coinciding onset ages patients. Specifically, highest fetal stage, indicating its vital development. Single‐cell an extensive neurons 1‐month‐old organoids, suggesting neurodevelopment. Significance causative DEE. spectrums potentially ranged lethality, DEE, NDD, mild epilepsy, depending on damaging effects caused

Язык: Английский

Процитировано

0
De novo heterozygous missense variants inATP11Aare associated with refractory focal epilepsy DOI

Zi-Long Ye,

Nan-Xiang Shen,

Xiang-Yun Luo

и другие.

Journal of Medical Genetics, Год журнала: 2025, Номер unknown, С. jmg - 110540

Опубликована: Апрель 4, 2025

Background ATP11A encodes an integral-membrane type IV P-type-adenosine triphosphatase that plays important role in neural development by maintaining membrane lipid asymmetry. de novo heterozygous missense variants have been reported to be associated with hypomyelinating leukodystrophy; however, the neurological symptoms of patients are often varying. In this study, we aimed explore relationship between and epilepsy. Methods Trio-based whole-exome sequencing was performed on focal Multiple bioinformatics analyses were used predict pathogenicity variants. Previously literature collected analyse relation phenotypes. Results Two identified two unrelated refractory epilepsy predicted pathogenic using multiple analyses. Then, six collected. Half (3/6) located on/near transmembrane regions (TMs) had more severe symptoms, while other half non-TM mild single indicating a correlation variant location phenotype. All showed progressively worsening conditions, potentially due gradually increased expression human brain over time. Conclusion This study suggested Missense variant-associated phenotypes range from epileptic seizures symptoms. It should noted potential.

Язык: Английский

Процитировано

0