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.
Original language | English (US) |
---|---|
Pages (from-to) | 1624-1627 |
Number of pages | 4 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 149 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2009 |
Keywords
- Clinical molecular diagnostics
- Exonic splice enhancer
- Mandibulofacial dysostosis
- RNA splicing
- Silent mutation
- TCOF1 protein
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)