Edition of 28 February 2020

A new study published in Annals of Neurology identified homozygous POPDC3 missense variants in 5 patients from 3 ethnically distinct families. Muscle weakness was proximal with adulthood onset in most patients and affected lower earlier than upper limbs. The Popeye domain containing 3 (POPDC3) gene encodes a membrane protein involved in cyclic adenosine monophosphate (cAMP) signaling. The study highlighted an important role of POPDC3 for skeletal muscle function and suggest that pathogenic variants in POPDC3 are responsible for a novel type of autosomal recessive limb girdle muscular dystrophy.

A new study published in the European Journal of Human Genetics identified three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before. The phenotypes of the described individuals are mainly characterized by axial endosteal hyperostosis, oligodontia, short stature, and mild facial dysmorphisms. These features largely fit within the spectrum of phenotypes caused by previously described biallelic variants in POLR3A, POLR3B, POLR1C, and POLR3K. These findings further expanded the spectrum of POLR3-related disorders and implicate that POLR3GL should be included in genetic testing if such disorders are suspected.