Clinical and functional characterization of two novel ZBTB20 mutations causing Primrose syndrome
2018
Primrose syndrome(PS) is a rare disorder characterized by
macrocephaly, tall stature, intellectual disability,
autistic traits, and disturbances of glucose metabolism with
insulin-resistant diabetesand distal muscle wasting occurring in adulthood. The disorder is caused by functional dysregulation of ZBTB20, a transcriptional repressor controlling energetic metabolism and developmental programs. ZBTB20 maps in a genomic region that is deleted in the 3q13.31
microdeletion syndrome, which explains the clinical overlap between the two disorders. A narrow spectrum of amino acid substitutions in a restricted region of ZBTB20 encompassing the first and second
zinc-fingermotifs have been reported thus far. Here, we characterize clinically and functionally the first truncating mutation [(c.1024delC; p.(Gln342Serfs*42)] and a missense change affecting the third
zinc-fingermotif of the
protein[(
c.1931C > T; p.(Thr644Ile)]. Our data document that both mutations have dominant negative impact on wild-type ZBTB20, providing further evidence of the specific behavior of PS-causing mutations on ZBTB20 function.
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