De novo variants in LDB1 are linked to distinct neurodevelopmental phenotypes determined by variant location and differing pathomechanisms

De novo variants in LDB1 were linked to distinct neurodevelopmental disorders (NDDs). N-terminal missense and truncating variants lead to loss of function and variable NDDs without brain anomalies, and C-terminal missense or truncating variants act through a dominant-negative mechanism and lead to NDDs with ventriculomegaly and organ anomalies.