Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay DOI Creative Commons
Katja Kobow, Samir Jabari, Tom Pieper

et al.

Acta Neuropathologica, Journal Year: 2020, Volume and Issue: 140(6), P. 881 - 891

Published: Sept. 26, 2020

Abstract Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration abnormal lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying development are not yet understood. About 40 genes have been associated PMG, copy number variations also described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here, we analyzed 26 patients employing array-based profiling formalin-fixed paraffin-embedded material. A series 62 well-characterized non-PMG malformations (focal dysplasia type 2a/b hemimegalencephaly), temporal lobe epilepsy, non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction hierarchical cluster analysis profiles showed formed distinct class. Copy from data identified uniform duplication spanning the entire long arm chromosome 1 7 out patients, which verified additional fluorescence situ hybridization analysis. In respective cases, about 50% nuclei center lesion were 1q triploid. No chromosomal imbalance seen adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, presented unilateral frontal or hemispheric without hemimegalencephaly, severe form intractable epilepsy seizure onset first months life, delay. Our results show among other according to their profile. One subset clinical features exhibits 1q.

Language: Английский

The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2 DOI Creative Commons
Abbe Lai, Aubrie Soucy, Christelle Moufawad El Achkar

et al.

Genetics in Medicine, Journal Year: 2022, Volume and Issue: 24(11), P. 2240 - 2248

Published: Aug. 23, 2022

Language: Английский

Citations

21
Shaping the cerebral cortex by cellular crosstalk DOI Creative Commons
Julie Stoufflet,

Sylvia Tielens,

Laurent Nguyen

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(13), P. 2733 - 2747

Published: June 1, 2023

Language: Английский

Citations

11
TUBB3 and KIF21A in neurodevelopment and disease DOI Creative Commons
Dharmendra Puri, Brenda J. Barry, Elizabeth C. Engle

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 4, 2023

Neuronal migration and axon growth guidance require precise control of microtubule dynamics microtubule-based cargo transport. TUBB3 encodes the neuronal-specific β-tubulin isotype III, TUBB3, a component neuronal microtubules expressed throughout life central peripheral neurons. Human pathogenic missense variants result in altered function cause errors either cranial and, to lesser extent, axons, or cortical organization, rarely both. Moreover, human KIF21A , which an anterograde kinesin motor protein that interacts directly with microtubules, alter can phenocopy variants. Here, we review reported variants, resulting phenotypes, corresponding functional studies both wildtype mutant proteins. We summarize evidence that, vitro mouse models, loss-of-function microtubule-kinesin interactions. Lastly, highlight additional might contribute our understanding relationship between specific tubulin isotypes proteins health disease.

Language: Английский

Citations

11
Exhaustive clinical examination of etiology and initial response to first‐line treatment in 577 children with infantile epileptic spasm syndrome children: A 5‐year retrospective observational study DOI Creative Commons
Lin Wan,

Wenrong Ge,

Guoyin Liu

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2024, Volume and Issue: 11(8), P. 2049 - 2062

Published: June 10, 2024

Abstract Objective Employing whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating potential associated factors, might improve short‐term responses first‐line treatment. Methods We retrospectively evaluated patients with IESS admitted for treatment between January 2018 June 2023. Clinical differences among etiological classifications clinical manifestations were analyzed. Variable selection using best subset method was performed, followed by logistic regression analysis identify factors influencing response. Results A total 577 included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities detected in 387 (67.1%). Patients as structural likelier have non‐spasms at initial seizure onset. 532 treatment; 273 received it first time our hospital (initial response rates: 30.1% 42.1%, respectively). The group had a lower proportion early‐onset seizures (≤3 months) than no‐response (11.3% vs. 23.7%, p < 0.01 11.3% 21.5%, = 0.03, Logistic indicated that earlier initiation higher likelihood an However, classification did not significant impact on Interpretation are more likely present non‐spasm Early is crucial; however, may be less favorable when occur early infancy.

Language: Английский

Citations

4
Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay DOI Creative Commons
Katja Kobow, Samir Jabari, Tom Pieper

et al.

Acta Neuropathologica, Journal Year: 2020, Volume and Issue: 140(6), P. 881 - 891

Published: Sept. 26, 2020

Abstract Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration abnormal lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying development are not yet understood. About 40 genes have been associated PMG, copy number variations also described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here, we analyzed 26 patients employing array-based profiling formalin-fixed paraffin-embedded material. A series 62 well-characterized non-PMG malformations (focal dysplasia type 2a/b hemimegalencephaly), temporal lobe epilepsy, non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction hierarchical cluster analysis profiles showed formed distinct class. Copy from data identified uniform duplication spanning the entire long arm chromosome 1 7 out patients, which verified additional fluorescence situ hybridization analysis. In respective cases, about 50% nuclei center lesion were 1q triploid. No chromosomal imbalance seen adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, presented unilateral frontal or hemispheric without hemimegalencephaly, severe form intractable epilepsy seizure onset first months life, delay. Our results show among other according to their profile. One subset clinical features exhibits 1q.

Language: Английский

Citations

32