Respiratory onset in an ALS family with L144F SOD1mutation

International audienceFamilial amyotrophic lateral sclerosis (FALS) cases linked to SOD1 mutations may sometimes present with unusual clinical features such as pure lower motor neuron involvement or sensory signs. We describe a FALS pedigree with the L144F SOD1 mutation in which all cases had respiratory involvement as a first symptom. Although atypical clinical features are not rare in ALS families, this is the first pedigree with respiratory-onset in three affected members. This unusual presentation led to delayed diagnosis in the proband and highlights the fact that respiratory-onset can occur in familial ALS cases carrying SOD1 mutation

Detection of irrigated and rainfed crops in temperate areas using Sentinel-1 and Sentinel-2 time series

International audienceThe detection of irrigated areas by means of remote sensing is essential to improve agricultural water resource management. Currently, data from the Sentinel constellation offer new possibilities for mapping irrigated areas at the plot scale. Until now, few studies have used Sentinel-1 (S1) and Sentinel-2 (S2) data to provide approaches for mapping irrigated plots in temperate areas. This study proposes a method for detecting irrigated and rainfed plots in a temperate area (southwestern France) jointly using optical (Sentinel-2), radar (Sentinel-1) and meteorological (SAFRAN) time series, through a classification algorithm. Monthly cumulative indices calculated from these satellite data were used in a Random Forest classifier. Two data years have been used, with different meteorological characteristics, allowing the performance of the method to be analysed under different climatic conditions. The combined use of the whole cumulative data (radar, optical and weather) improves the irrigated crop classifications (Overall Accuary (OA) ≈ 0.7) compared to the classifications obtained using each data separately (OA < 0.5). The use of monthly cumulative rainfall allows a significant improvement of the Fscore of irrigated and rainfed classes. Our study also reveals that the use of cumulative monthly indices leads to performances similar to those of the use of 10-day images while considerably reducing computational resources

Facial-onset sensory-motor neuronopathy, a rare variant of Huntington’s disease or chance association?

Objectives: To describe a patient with facial-onset sensory-motor neuronopathy (FOSMN) that later developed Huntington&rsquo;s disease (HD). Case report: A 62-year-old woman complained of progressive dysphagia 8 years before referral. At initial evaluation, there was excessive salivation, dysphagia, and sensory-motor trigeminal impairment. Denervation was noted on the upper limbs and the tongue. Blink reflexes were abolished. Genetic study of amyotrophic lateral sclerosis (ALS)-related genes was normal. She was diagnosed with FOSMN syndrome. Her clinical state progressively worsened with corneal anesthesia, severe denutrition, right arm and axial weakness. Seven years after referral, she was unable walk and developed generalized chorea. Abnormal huntingtin gene repeat expansion confirmed the diagnosis of HD. She died 16 years after onset of dysphagia. Conclusion: Cases with both HD and ALS have already been reported but not FOSMN and HD, to our knowledge. Some FOSMN cases have been linked to ALS-related gene mutations and HD phenocopies have been associated with C9ORF72 repeat expansions. Recently, huntingtin repeat expansions were described in the ALS population. Although a chance association cannot be excluded, data from the literature are in favor of a pathogenic relationship between FOSMN and HD in this particular case. We suggest that huntingtin gene be more systematically studied in patients with FOSMN

Detecting Irrigation Events Using Sentinel-1 Data

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Reversible sub-acute motor neuron syndrome after mushroom intoxication masquerading as amyotrophic lateral sclerosis

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Compound heterozygous P67S/D91A SOD1 mutations in an ALS family with apparently sporadic case

International audienceObjectives: To describe a family with heterozygous P67S and D91A SOD1 mutations. Methods: The ALS profile of the proband was described. SOD1 gene sequencing was performed in the proband and his children. Results: The affected individual presented with progressive left peripheral facial palsy and slow progression with late limb involvement. Unequivocal upper and lower motor neuron signs were present, together with diffuse denervation at myography. The absence of trigeminal involvement excluded a FOSMN syndrome. Pedigree analysis did not show any other ALS case in the family. Genetic analysis of this patient showed P67S and D91A SOD1 mutations. The genetic analysis of the children showed that the mutations were each one carried by a different chromosome. Conclusions: P67S SOD1 mutation has been described in several ALS cases, either with familial or apparently sporadic ALS. The mutation is located in a mutational hotspot and was predicted pathogenic by in silico prediction software. The study of phylogenetic data show that at this codon, the proline is highly conserved throughout species reinforcing causality. Conversely, the D91A variant is known to have a recessive influence. Unilateral motor facial involvement, even after several years, in an ALS patient is unusual. The present case with compound heterozygosity and unusual onset in a patient with apparently sporadic ALS, widens the clinical spectrum of the disease and adds further arguments to support the systematic genetic screening of all ALS cases in referral ALS clinics

Les répétitions intermédiaires GGGGCC du gène C9ORF72 ne sont pas un facteur de risque de SLA.

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Liver X Receptor Genes Variants Modulate ALS Phenotype

International audienceAmyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. Phenotype of ALS patients is highly variable and may be influenced by modulators of energy metabolism. Recent works have implicated the liver X receptors α and β (LXRs), either in the propagation process of ALS or in the maintenance of MN survival. LXRs are nuclear receptors activated by oxysterols, modulating cholesterol levels, a suspected modulator of ALS severity. In a cohort of 438 ALS patients and 330 healthy controls, the influence of LXR genes on ALS risk and phenotype was studied using single nucleotide polymorphisms (SNPs). The two LXRα SNPs rs2279238 and rs7120118 were shown to be associated with age at onset in ALS patients. Consistently, homozygotes were twice more correlated than were heterozygotes to delayed onset. The onset was thus delayed by 3.9 years for rs2279238 C/T carriers and 7.8 years for T/T carriers. Similar results were obtained for rs7120118 (+2.1 years and +6.7 years for T/C and C/C genotypes, respectively). The LXRβ SNP rs2695121 was also shown to be associated with a 30% increase of ALS duration (p = 0.0055, FDR = 0.044). The tested genotypes were not associated with ALS risk. These findings add further evidence to the suspected implication of LXR genes in the disease process of ALS and might open new perspectives in ALS therapeutics

Intermediate C9orf72 repeat numbers are not ALS risk factors

International audienceIntroduction:Amyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. The C9orf72 repeat expansion is the most common genetic cause of the disease. Initial findings have set the pathogenic cut-off to 30 repeat. However, intermediate repeat numbers between 16 and 30 have also been proposed to be associated with ALS risk. As most studies rely on ALS patients, we performed a case-control study in a French cohort to understand the involvement of intermediate repeats on the ALS risk.Methods:In a cohort of 412 C9orf72-negative sporadic ALS patients and 327 healthy controls, the C9orf72 repeat number was assessed by Repeat-Primed PCR.Results:The most frequent alleles were two, five and eight repeats both in ALS and control groups. The highest repeat number was 22 in controls and 26 in patients. The allelic distribution was not significantly different between both groups.Conclusions:These findings show a lack of association between C9orf72 intermediate repeat numbers and the risk of developing ALS. These data suggest that repeat numbers below 30 are not an ALS risk factor in the French population and confirms the definition of theC9orf72 pathogenic cut-off

Les répétitions intermédiaires GGGGCC du gène C9ORF72 ne sont pas un facteur de risque de SLA.

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