The Alagille syndrome (AGS), a congenital disorder affecting liver, heart, skeleton and eye in association with a typical face, is an autosomal dominant disease with nearly complete penetrance and variable expression. AGS is caused by mutations in the developmentally important JAG1 gene. In our mutation screening, where 61 mutations in JAG1 were detected, we identified five cases where mosaicism is present. Our results point to a significant frequency of mosaicism for JAG1 mutations in AGS of more than 8.2%. Because mosaicism may be associated with a very mild phenotype, the appropriate diagnosis of AGS and consequently the determination of the recurrence risk can be complicated.
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We gratefully acknowledge the technical assistance of Mechthild Gräber and the support of many physicians who provided AGS samples and clinical data. We especially want to express our gratitude to Dr G Matthijs for the mediation of AGS case 4. This study was supported by the DFG.
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Giannakudis, J., Röpke, A., Kujat, A. et al. Parental mosaicism of JAG1 mutations in families with Alagille syndrome. Eur J Hum Genet 9, 209–216 (2001). https://doi.org/10.1038/sj.ejhg.5200613
- Alagille syndrome
- JAG1 mutation
- mild phenotype
- chromosome 20
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