Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy
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For some time now, drugs with different mechanisms of action have been available for the treatment of spinal muscular atrophy that can significantly influence the course of the disease. If left untreated, this neuromuscular disease is always progressive and the most severe form, SMA type 1, usually leads to death within 24 months. The genetic defect lies in the survival motor neuron 1 gene (SMN1 gene). This leads to a loss of SMN1 protein and thus to the death of motor neurons. In all patients, the SMN2 gene, which can only produce about 10% functional protein, is present in different numbers of copies and influences the clinical severity of the disease. Smooth transitions between the individual types are observed. The first drug approved for SMA is Spinraza®, an antisense oligonucleotide that is administered intrathecally, changes mRNA splicing, and thus leads to increased production of SMN2 protein. The second approved drug is Zolgensma®, a gene replacement therapy in which the SMN1 gene is introduced into the body as a single infusion using a virus vector, in order to produce functioning SMN protein. Also about to be approved is Risdiplam®, a so-called ?small molecule? and, like Spinraza®, it targets the SMN2 gene. The advantage is that it can be taken orally. In all studies on these drugs it could be shown that starting as early as possible, preferably presymptomatically, produced the best motor score results for the patients. Newborn screening could detect the affected children before symptoms start.