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RNA polymerase III (Pol III) is an essential 17-subunit complex responsible for the transcription of small housekeeping RNAs such as transfer RNAs and 5S ribosomal RNA. Biallelic variants in four genes (POLR3A, POLR3B, and POLR1C and POLR3K) encoding Pol III subunits have previously been found in individuals with (neuro-) developmental disorders. In this report, we describe three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before. Using whole exome sequencing in a monozygotic twin and an unrelated individual, we detected homozygous and compound heterozygous POLR3GL splice acceptor site variants. RNA sequencing confirmed the loss of full-length POLR3GL RNA transcripts in blood samples of the individuals. 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 expand the spectrum of POLR3-related disorders and implicate that POLR3GL should be included in genetic testing if such disorders are suspected.


Paulien A Terhal, Judith M Vlaar, Sjors Middelkamp, Rutger A J Nievelstein, Peter G J Nikkels, Jamila Ross, Marijn Créton, Jeroen W Bos, Elsbeth S M Voskuil-Kerkhof, Edwin Cuppen, Nine Knoers, Koen L I van Gassen. Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia. European journal of human genetics : EJHG. 2020 Jan;28(1):31-39

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PMID: 31089205

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