De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders.

ABSTRACT: Recurrent somatic variants in SPOP are cancer specific; endometrial and prostate cancers result from gain-of-function and dominant-negative effects toward BET proteins, respectively. By using clinical exome sequencing, we identified six de novo pathogenic missense variants in SPOP in seven individuals with developmental delay and/or intellectual disability, facial dysmorphisms, and congenital anomalies. Two individuals shared craniofacial dysmorphisms, including congenital microcephaly, that were strikingly different from those of the other five individuals, who had (relative) macrocephaly and hypertelorism. We measured the effect of SPOP variants on BET protein amounts in human Ishikawa endometrial cancer cells and patient-derived cell lines because we hypothesized that variants would lea

SUBMITTER: Nabais Sa MJ 

PROVIDER: S-EPMC7058825 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature