Sébastien Lévesque's research while affiliated with Centre hospitalier universitaire de Sherbrooke and other places

... Moreover, some genetic variants lead to pseudodeficiency, which is characterized by patients having low enzymatic activity in blood but not producing any muscle damage. 15 ...

... Two missense variants in the CAPN15 gene were assessed in a patient displaying irido-choroidal coloboma associated with a mild developmental delay (A106). Biallelic CAPN15 variants are associated to the oculogastrointestinal-neurodevelopmental syndrome (OMIM #619318), firstly reported in 2020 by Zha et al. [24]. Missense variants are known to be exclusively related to microphthalmia and/ or coloboma [25]. ...

... The most common approaches in NMD genetic diagnostics comprise targeted gene panel (TGP), including clinical exome, and/or whole exome sequencing (WES). It has been revealed that the diagnostic yield of TGP may differ from 15.1% to even 49.3%, depending on the number of study groups and the number of analyzed genes [8][9][10][11]. However, there is a possibility to increase the utility by using a comprehensive TGP, which involves all updated known disease-causing genes with high coverage of these target genes [12]. Barbosa-Gouveia et al. (2022) confirmed that increasing the number of causative genes from 278 to 324 enables to obtain a higher diagnostic rate from 31 to 40% in 268 NMD patients [13]. ...

... Although multisystemic involvement has been reported, central nervous system and cardiac involvement are prominent [7]. HSD10 disease is characterized by metabolic decompensation episodes, lethargy, restlessness, global developmental delay, hypotonia, epilepsy, encephalopathy, progressive psychomotor retardation (frequently after infection or vaccination), microcephaly, movement disorder, gait abnormality, spasticity, visual and hearing impairment, cardiomyopathy (hypertrophic or dilate), speech difficulty, intellectual disability, learning difficulties, autistic features, and behavioral abnormalities [2][3][4][6][7][8][9][10]. ...

... Neonatal transient hyperthyrotropinemia is generally readily attributed to iodine overload, as high iodine levels block TH synthesis by inhibiting organification or to the passage of antithyroid antibodies or ATDs across the placenta; most cases resolve rapidly without the need for levothyroxine treatment (38)(39)(40). Some patients may also present transient CH due to genetic disorders, such as DUOX2/DUOXA2 gene mutation, requiring transient levothyroxine treatment (41). Transient hypothyroxinemia due to an immature hypothalamic-pituitarythyroid axis is frequently observed in preterm neonates (42). ...

... We cloned ACSF2 and ACSF3 cDNA, overexpressed the proteins in COS-1 cells, and demonstrated that both had ACS enzyme activity [2]. While ACSF3 showed a weak ability to activate a 24-carbon very long-chain FA, it was subsequently characterized as malonyl-CoA and methylmalonyl-CoA synthetase [8,9]. Mutations in ACSF3 are causative of combined malonic and methylmalonic aciduria [9]. ...

... The origin of the CMAMMA in affected patients is elucidated by the reduced binding of mutant ZBTB11 to the ACSF3 promoter, as demonstrated by the findings presented by Sumathipala and colleagues. 1 Furthermore, it is important to mention that individuals who have a deficiency in ACSF3 (Acyl-CoA synthetase family, member 3, OMIM*614245) also demonstrate CMAMMA. 15,16 Considering this finding, it may be necessary to include other rare neurodevelopmental disorders in the differential diagnosis, such as methylmalonate semialdehyde dehydrogenase (OMIM 614105) deficiency. This autosomal recessive disorder is caused by variants in the ALDH6A1 gene and is associated with numerous metabolic abnormalities, including methylmalonic aciduria, cataracts, varying degrees of ID, and MRI abnormalities, including delayed myelination and a thin corpus callosum. ...

... Automated analysis tools aim to computationally prioritize variants suspected to be pathogenic based on structured phenotype terms provided by the user. These methods have been reported to increase diagnostic yield and the efficiency of analysis 22,68,69 . However, their sensitivity and specificity remain insufficient to replace the role of a human analyst 70,71 . ...

... An additional 10 knowledge items were added to the post-counselling knowledge scale, composed of 22 items (Q2), α =0.851. The knowledge items were compiled from earlier study (Fan et al. 2018) and items newly developed by the research team for the purpose of this study; they intended to assess knowledge of key concepts regarding RGCS, risks, and reproductive options (Supplementary). A knowledge score (0-22) was calculated for each participant from their responses to the knowledge items. ...

... In most of the ICA genes, pathogenic variants cause primary cardiomyopathy or arrhythmia; however, a small number of genes are associated with syndromic disorders. Recurrent and founder disease-causing variants have been described in some genes [5][6][7]; however, many variants appear to be novel, or private to a family. While there are several well-established ICA genes, there are also many genes where the genotype/phenotype relationship is less definitive [8][9][10][11][12][13]. ...