Publications by authors named "Xavier Le Guillou"
Article Synopsis
- RORA is a gene linked to the development and function of the cerebellum, and this study explores the largest group of individuals with RORA-related neurodevelopmental disorders (RORA-NDD).
- The study involved 40 participants with various pathogenic variants of RORA, revealing a range of clinical features including developmental and intellectual disabilities, as well as cerebellar symptoms that can vary in onset and severity.
- Findings indicate that certain missense variants are associated with more severe cerebellar issues, and common elements of RORA-NDD include developmental disabilities, cerebellar symptoms, and different types of myoclonic epilepsy.
Article Synopsis
- SCN5A gene variants are linked to various cardiac electrical disorders, but they can also result in complex phenotypes like overlap syndromes, which haven't been thoroughly studied.
- The study analyzed DNA from over 13,500 patients with a focus on those carrying pathogenic SCN5A variants, finding that most were tied to well-defined conditions like Brugada syndrome and long QT syndrome.
- About 19% of the variants were associated with complex phenotypes, and only a small number (8 out of 9,960 patients) showed a potential link to dilated cardiomyopathies (DCM), suggesting it's a rare association.
Article Synopsis
- Duplications of the 3q29 chromosomal region are rare genetic variations linked to diverse neurodevelopmental disorders, often causing learning disabilities and neuropsychiatric issues.
- A study involving 31 families revealed different sizes of 3q29 duplications: 14 recurrent, 8 overlapping, and 9 smaller ones, with some patients showing additional genetic factors influencing their conditions.
- Most patients exhibited mild neurodevelopmental disorders, with many duplications being inherited and associated with low rates of intellectual disabilities, suggesting that severe cases might require more detailed genetic examination.
Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions.
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- The study investigates the prevalence and effects of pathogenic variants in a specific gene related to cardiomyopathy and sudden cardiac death among patients.
- Out of 9,516 tested individuals, 31 were found to carry pathogenic variants, mostly presenting with dilated cardiomyopathy, with some also experiencing severe cardiac issues.
- Although the overall prognosis for dilated cardiomyopathy in variant carriers seems favorable, severe conditions and early onset were noted, especially in those with double variants.
Background: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.
Objectives: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.
ANK2 loss-of-function variants are associated with epilepsy, and lead to impaired axon initial segment plasticity and hyperactive network activity in hiPSC-derived neuronal networks.
Hum Mol Genet
July 2023
Article Synopsis
- The study investigates a new neurodevelopmental syndrome linked to loss-of-function variants in the ANK2 gene, associated with conditions like intellectual disability and autism.
- Researchers used CRISPR technology to create human-induced pluripotent stem cells (hiPSCs) with these genetic variants, then differentiated these cells into neurons for further examination.
- Findings revealed that ANK2-deficient neurons exhibited hyperactivity and lack of synchronization within neuronal networks, along with structural changes that affect their function and adaptability.
The Integrator complex is a multi-subunit protein complex that regulates the processing of nascent RNAs transcribed by RNA polymerase II (RNAPII), including small nuclear RNAs, enhancer RNAs, telomeric RNAs, viral RNAs, and protein-coding mRNAs. Integrator subunit 11 (INTS11) is the catalytic subunit that cleaves nascent RNAs, but, to date, mutations in this subunit have not been linked to human disease. Here, we describe 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.
View Article and Find Full Text PDFPurpose: Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder.
Methods: Cases with YWHAE variants were collected through international data sharing networks.
Article Synopsis
- Variants in the PRSS1 and PRSS2 genes are linked to chronic pancreatitis (CP), prompting research into whether a deletion variant affecting two trypsinogen pseudogenes (PRSS3P2 and TRY7) might influence CP risk.
- A study analyzed this deletion in over 4,000 participants from different countries and found that it is associated with a protective effect against CP, especially in French, German, and Japanese populations.
- The research suggests that the deletion enhances the function of remaining genes, leading to regulated PRSS2 expression, which could be crucial in understanding CP susceptibility.
Purpose: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown.
Method: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID).
Results: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.
Background: The recently recommended single lead-based criterion for the diagnosis of Brugada syndrome may lead to overdiagnosis of this disorder and overestimation of the risk of sudden cardiac death.
Aim: To investigate the value of a single-lead diagnosis in patients with Brugada syndrome and a spontaneous type 1 electrocardiogram.
Methods: Consecutive patients with Brugada syndrome were included in a multicentre prospective registry; only those with a spontaneous type 1 electrocardiogram were enrolled.