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Updated: Jun 22, 2026
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
A synonymous mutation in TCOF1 causes Treacher Collins syndrome due to mis-splicing of a constitutive exon
D Macaya1, S H Katsanis, T W Hefferon
1Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Abstract:
Interpretation of the pathogenicity of sequence alterations in disease-associated genes is challenging. This is especially true for novel alterations that lack obvious functional consequences. We report here on a patient with Treacher Collins syndrome (TCS) found to carry a previously reported mutation, c.122C > T, which predicts p.A41V, and a novel synonymous mutation, c.3612A > C. Pedigree analysis showed that the c.122C > T mutation segregated with normal phenotypes in multiple family members while the c.3612A > C was de novo in the patient. Analysis of TCOF1 RNA in lymphocytes showed a transcript missing exon 22. These results show that TCS in the patient is due to haploinsufficiency of TCOF1 caused by the synonymous de novo c.3612A > C mutation. This study highlights the importance of clinical and pedigree evaluation in the interpretation of known and novel sequence alterations.
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