HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.

ABSTRACT: The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mechanisms that are not known. Here, we report four unrelated individuals who have truncating or missense variants in the same C-terminal region of hnRNPR and who have multisystem developmental defects including abnormalities of the brain and skeleton, dysmorphic facies, brachydactyly, seizures, and hypoplastic external genitalia. We further identified in the literature a fifth individual with a truncating variant. RNA sequencing of primary fibroblasts reveals that these HNRNPR va

SUBMITTER: Duijkers FA 

PROVIDER: S-EPMC6556882 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature