LAUSR

gous de novo nonsense variant in CAMK4: NM_001744.4: c.940C>T, p.Gln314* as the only plausible candidate. This variant, absent from population-reference databases (gnomAD, inhouse exomes), was located fewer than 50 nucleotides upstream of the last exon–exon boundary and therefore most likely escaped from the nonsense-mediated decay pathway (Fig. 1). Like the previously identified splice-site variants (c.981+1G>A and c.981 +1G>T; Fig. 1), the c.940C>T (p.Gln314*) substitution was expected to give rise to a truncated regulatory domain–deficient protein with potential gain-of-function behavior. Notably, gainof-function effects have been demonstrated for the patient-derived splice-site alteration c.981+1G>A (p.Lys303Serfs*28) and a similar in vitro–engineered truncation mutant (CaMKIV in functional experiments performed by Chatila and colleagues). Unfortunately, functional assessment of the c.940C>T (p.Gln314*) variant was not possible because of the unavailability of a patient-specific cell line. The patient described here exhibited significant phenotypic overlap with our recently published individuals with CAMK4 splice-site variants, including delayed milestone attainment, intellectual disability, behavioral issues, autism, and abnormal hyperkinetic movements (Table S1). In all 3 patients, neurodevelopmental disability was accompanied by insidious onset of dystonia and chorea 3 to 20 years after the appearance of initial symptoms. Together, our findings consolidate an association between de novo clustered variants in CAMK4 and an autosomaldominant neurodevelopmental trait that can manifest with prominent movement disorders. This genetic entity should be considered in the differential diagnosis of choreodystonic syndromes with coexisting neurocognitive and behavioral problems.