PubMed · 8581649
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M Tsuda. 1995. [Chromosomal abnormalities].. https://pubmed.ncbi.nlm.nih.gov/8581649/
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PURPOSE: Alagille syndrome (ALGS) is an autosomal dominantly inherited disorder primarily caused by mutations in the Jagged Canonical Notch Ligand 1 (JAG1) gene. Although many pluripotent stem cells are well established, no patient-derived stem cells from exfoliated deciduous teeth (SHED) have been developed. In this study, we aimed to establish SHED from an ALGS patient carrying a heterozygous JAG1mut mutation. METHODS: We isolated SHED from a deciduous tooth of an ALGS patient with a heterozygous JAG1 mutation (ALGS-SHED) by the colony-forming unit-fibroblast (CFU-F) method. We then compared the characteristics of ALGS-SHED and healthy donor-derived control SHED (CONT-SHED). RESULTS: ALGS-SHED displayed mesenchymal stem cell features as indicated by CFU-F formation, immunophenotype, and mesenchymal multipotency into adipocytes, chondrocytes, and osteoblasts. ALGS-SHED showed reduced population doubling capacity and exhibited induced chondrogenic potency and diminished osteogenic potency, but similar hepatic potency. ALGS-SHED damaged in situ potency to form bile duct-like tubular structures in the livers of chronically CCl4-injured mice. CONCLUSIONS: We successfully established ALGS-SHED from an ALGS patient carrying a heterozygous JAG1 mutation. Our established ALGS-SHED may represent a potential model for studying ALGS involving a JAG1 mutation.
Mutations in Jagged1 cause Alagille syndrome (AGS), a pleiotropic disorder with involvement of the liver, heart, skeleton, eyes, and facial structures. Cardiac defects are seen in more than 95% of AGS patients. Most commonly these are right-sided defects ranging from mild peripheral pulmonic stenosis to severe forms of tetralogy of Fallot. AGS demonstrates highly variable expressivity with respect to all of the involved systems. This leads us to hypothesize that defects in Jagged1 can be found in patients with presumably isolated heart defects, such as tetralogy of Fallot or pulmonic stenosis. Two patients with heart defects of the type seen in AGS and their relatives were investigated for alterations in the Jagged1 gene. Jagged1 was screened by a combination of cytogenetic and molecular techniques. Patient 1 was studied because of a four-generation history of pulmonic stenosis. Molecular analysis showed a point mutation in Jagged1 in the patient and her mother. Patient 2 was investigated owing to the finding of tetralogy of Fallot and a "butterfly" vertebra on chest radiograph first noted at age 5 years. She was found to have a deletion of chromosome region 20p12 that encompassed the entire Jagged1 gene. The identification of these two patients suggests that other patients with right-sided heart defects may have subtle findings of AGS and Jagged1 mutations.
We present a case of macromastia in a newborn with Alagille syndrome. A review of the literature failed to find any prior reports of this findings in Alagille syndrome patients. We propose that this patient's macromastia may be related to her liver failure and abnormal estrogen metabolism.