Supplementary Material for: First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the <i>TCOF1</i> gene and follows autosomal dominant inheritance. Recently, mutations in the <i>POLR1D </i>and<i> POLR1C</i> genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout <i>TCOF1</i>. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within <i>TCOF1</i> lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in <i>TCOF1</i>, <i>POLR1D</i> and <i>POLR1C</i>. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within <i>TCOF1</i>. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by <i>TCOF1.</i>