The recursive violence of reform: A century of failed interventions in migrant farmworker housing.

Aminoacyl-tRNA synthetases (ARSs) are crucial enzymes in protein synthesis, ensuring accurate pairing of amino acids to their specific tRNA molecules [,]. At present, there are 37 ARS genes known in humans, with 18 functioning in the cytoplasm, 17 in the mitochondria, and 2 that serve both compartments []. Pathogenic mutations in 31 genes have been associated with neurodevelopmental disorders [], cancer [], and autoimmune diseases []. () (MIM: 192150) encodes an enzyme that is fundamental in the attachment of valine to valine-tRNA []. Pathogenic mutations in are associated with ‘Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy’ (NDMSCA) (MIM:617802) []. Karaca et al. first reported two pathogenic variants, NM_006295.2: c.2653C>T p.(Leu885Phe) and c.3173G>A p.(Arg1058Gln), in two consanguineous families with epileptic encephalopathy []. Additional variants in patients with similar clinical findings are associated with biallelic variants in [–]. studies using patient-derived cell lines, including enzymatic and yeast complementation assays, indicate that recessive mutations likely result in a loss-of-protein function. This is consistent with them being loss-of-function (LoF) alleles. Furthermore, a knockout zebrafish model mirrors key human disease characteristics, exhibiting microcephaly and epileptiform activity []. In this study, we identified a total of 16 different variants in 10 unrelated families, this includes 10 variants not previously documented in existing literature – eight missense (p.(Leu16Arg), p.(Pro51Ser), p.(Met296Val), p. (Arg404Gln), p.(His566Tyr), p.(Arg665Trp), p.(Ser866Cys), and p. (Asp920Asn)), one synonymous (p.(Leu631)) and one premature stop codon (p.(Trp790*). This work contributes to a broader understanding of the mutational spectrum and elucidates the genotype-phenotype correlation in NDMSCA. Families were recruited through international collaborations and the use of GeneMatcher. The identification of the seven families described in this report involved exome sequencing (ES) and the collaborative sharing of data between genetic centers worldwide, with GeneMatcher being instrumental in patient recruitment for this study. The study was approved by the Research Ethics Committee Institute of Neurology University College London (IoN UCL) (07/Q0512/26) and the local Ethics Committees of each participating center.