We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy.
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We express our sincere gratitude to the cases, their parents and other family members for their participation in this study, as well as to the clinicians for sending blood samples. We want to thank the Laboratory for Diagnostic Genome Analysis (LDGA) in Leiden and the Forensisch Laboratorium voor DNA Onderzoek (FLDO), as well as the TCS team in Essen and Regensburg for their excellent technical assistance and Ivo Fokkema for his help with constructing the Leiden Open Variation Databases (LOVD). This work was part of the CRANIRARENetwork funded through a grant from the German Ministry of Research and Education to D.R.L. and D.W. (BMBF 01GM0802). The financial support of the National Institutes of Health Research Manchester Biomedical Research Centre and the Healing Foundation to J.D. and M.J.D. is gratefully acknowledged.
The authors declare no competing financial interests.
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