Novel JAG1 variants found in two cases of Alagille syndrome

A new study has identified novel JAG1 gene mutations in 2 cases of Alagille syndrome (ALGS). The study underscores the challenges in accurately diagnosing ALGS due to its variable phenotypic expression, leading to potential misdiagnoses or underdiagnoses.

The first case involved a patient with a unique p.Pro325Leufs*87 variant, who was diagnosed at the age of 2 months. Despite the initial challenges, this individual exhibited a favorable prognosis, along with an unexpected manifestation of congenital hypothyroidism.

The second patient was incorrectly diagnosed with liver structural abnormalities before the age of 2. This misdiagnosis led to extensive treatment and delays in language acquisition. The study suggests that the language delays may be linked to SNAP25 haploinsufficiency, showcasing the diverse ways ALGS can manifest.

The identification of ALGS remains a complex task, underscoring the significance of early detection and genetic testing for effective patient management. The variant p.Pro325Leufs*87 discovered in the first case is distinct from reported variants associated with congenital hypothyroidism in ALGS patients, emphasizing the clinical and genetic complexity of the syndrome.

Reference
Feng X, Ping J, Gao S, et al. Novel JAG1 variants leading to Alagille syndrome in two Chinese cases. Sci Rep. 2024;14(1):1812. doi: 10.1038/s41598-024-52357-0. PMID: 38245625; PMCID: PMC10799942.

Rare Disease 360^® is the Official Media Partner and Official Publication of The Alagille Syndrome Alliance (Alagille.org).