Publications by authors named "L Guillot-Noel"
Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.
View Article and Find Full Text PDFMultiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli.
Neurol Neuroimmunol Neuroinflamm
November 2024
Article Synopsis
- In multiple sclerosis (MS), immune cells, particularly macrophages, play a dual role in damaging myelin and potentially aiding in its repair, but abnormalities in macrophage responses in MS patients may worsen inflammation and hinder repair processes.
- The study compared the activation of monocytes from MS patients and healthy controls, utilizing RNA sequencing and metabolomics to analyze differences in macrophage behavior and functionality.
- Findings revealed that MS macrophages preferentially activate in a proinflammatory manner, show reduced myelin processing ability, and promote the differentiation of cells toward astrocytes rather than oligodendrocytes, indicating a metabolic dysfunction and persistent inflammatory profile in MS patients.
Biallelic variants in the ERLIN1 gene were recently reported as the cause of two motor neuron degeneration diseases, SPG62 and a recessive form of amyotrophic lateral sclerosis. However, only 12 individuals from five pedigrees have been identified so far. Thus, the description of the disease remains limited.
View Article and Find Full Text PDFBackground: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.
Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.
Article Synopsis
- Molecular diagnosis of spinocerebellar ataxia typically involves a step-by-step approach, but genome sequencing and the ExpansionHunter tool allow for more streamlined detection of repeat expansions in a single step.
- ExpansionHunter has been validated for detecting repeat expansions in exome sequencing and showed 100% sensitivity and specificity when compared with traditional methods for certain loci.
- The study identified 22 additional pathogenic expansions in 498 sample exomes, although it did underestimate the size of larger expansions, indicating the need for careful interpretation of results.