Abstract
Abstract
Background
Alagille syndrome (ALGS) is a rare autosomal dominant multisystem disorder that affects the liver, heart, eyes, vertebrae, and kidneys and is associated with characteristic facies. This work aimed to study the spectrum of the clinical features of ALGS in an Egyptian cohort of patients in conjunction with partial sequencing of the JAG1 gene.
Methods
This study included 17 pediatric ALGS patients diagnosed on clinical grounds: facial features, cholestatic liver disease, and cardiac, vertebral, and ocular findings. Molecular analysis was conducted in 10 selected exons of the JAG1 gene.
Results
The clinical features of ALGS included cholestatic liver disease (100%), facial dysmorphism (100%), cardiac abnormalities (88.2%), butterfly vertebrae (64.7%), posterior embryotoxon (35.2%), poor growth (41%), xanthomata (11.8%), and hiatus hernia (11.8%). Five novel pathogenic JAG1 mutations were identified in this study, including two nonsense mutations, one splicing mutation, one frameshift insertion, and one frameshift deletion. In two patients, the mutations were confirmed to be de novo, as the mutations could not be detected in both parents.
Conclusion
Five novel JAG1 pathogenic variants were identified in this study. This is the first molecular study to report pathogenic mutations in the JAG1 gene within an Egyptian cohort of children with ALGS.
Publisher
Springer Science and Business Media LLC
Reference34 articles.
1. Alagille D, Odièvre M, Gautier M, Dommergues JP (1975) Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr 86:63–71
2. Alagille D, Estrada A, Hadchouel M, Gautier M, Odièvre M, Dommergues JP (1987) Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 110:195–200
3. Brennan A, Kesavan A (2017) Novel heterozygous mutations in JAG1 and NOTCH2 genes in a neonatal patient with Alagille syndrome. Case Reports in Pediatrics, 1368189
4. Bucuvalas JC, Horn JA, Carlsson L, Balistreri WF, Chernausek SD (1993) Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature. J Clin Endocrinol Metab 76:1477–1482
5. Chen Y, Liu X, Chen S, Zhang J, Xu C (2019) Targeted sequencing and RNA assay reveal a noncanonical JAG1 splicing variant causing Alagille syndrome. Front Genet 10:1363
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献