Combining our cohort of 86 novel JAG1 and three novel NOTCH2 variants with previously published data (totaling 713 variants), we present the most comprehensive pathogenic variant overview for Alagille syndrome.
JAGGED1, a membrane-bound NOTCH ligand, is required for normal craniofacial development, and Jagged1 mutations in humans are known to cause Alagille Syndrome, which is associated with cardiac, biliary, and bone phenotypes and these children experience increased bony fractures.
Although genetic tests for liver cholestatic diseases were performed with negative results for Alagille syndrome (JAG1 and NOTCH2), a de-novo missense mutation of HNF1β gene was detected.
In this case report, we document a case of Alagille syndrome with an atypical clinical and histopathologic presentation and subsequent identification of a novel JAG1 missense mutation.
Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, mainly caused by haploinsufficiency of the Notch ligand jagged1.
Mice with a missense mutation (H268Q) in Jag1 (Jag1<sup>+/Ndr</sup> mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1<sup>Ndr/Ndr</sup> mice).
Mice with a missense mutation (H268Q) in Jag1 (Jag1<sup>+/Ndr</sup> mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1<sup>Ndr/Ndr</sup> mice).
The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations that cause: (a) Alagille syndrome (ALGS), a genetic disorder where NOTCH signaling pathway mutations impair bile duct formation, which has substantial variability in its associated clinical features; and (b) Tetralogy of Fallot (TOF), which is the most common form of a complex congenital heart disease, and is associated with several different heritable disorders.
Molecular genetic characterization of a prenatally detected de novo interstitial deletion of chromosome 20p (20p12-p13) encompassing JAG1 and a literature review of prenatal diagnosis of Alagille syndrome.
Here, we report a unique case of a patient diagnosed with Alagille syndrome who was found to have a previously undescribed frameshift pathogenic mutation in the JAG1 gene and who presented with xanthomatosis and levels of hypercholesterolemia more than 2 times higher than those previously reported in the literature.
Angiogenic defects secondary to gene mutations of JAG1 and NOTCH2, causing arterial anomalies in Alagille syndrome (AGS), are well described in the literature.
We analysed 30 subjects with Alagille syndrome, nine with incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9 subjects with incomplete Alagille syndrome.
JAG1 mutations have been associated with several disorders including the multi-system dominant disorder Alagille syndrome, and some cases of tetralogy of Fallot (although these may represent variable expressivity of Alagille syndrome).
Heterozygous JAG1 variants are known to account for Alagille syndrome type 1 (ALGS1), a rare multisystemic developmental disorder characterized by variable expressivity and penetrance.
Haploinsufficiency for the Notch ligand JAG1 in humans results in an autosomal-dominant, multisystem disorder known as Alagille syndrome, which is characterized by a congenital cholangiopathy of variable severity.