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Alagille syndrome (ALGS) is an autosomal dominant disorder which is mainly caused by JAG1 gene mutation and can affect multiple systems including the liver, heart, eyes, skeleton and face. This paper reports the clinical and genetic features of an ALGS patient. A 2-year-and-9-month-old boy was referred to the hospital with the complaint of abnormal liver function and heart murmur discovered over two years. Jaundice of the skin and sclera was not observed. The child had a prominent forehead, left esotropia, depressed nasal bridge and micromandible. The two lungs were clear on auscultation, but a systolic cardiac murmur of grade 2/6 could be heard between the 2nd and 3rd intercostal space at the left sternal border. Neither abdominal distension nor enlarged liver or spleen was discovered. X-ray radiography uncovered butterfly malformation of the 6th and 8th thoracic vertebrae. Serum biochemistry analysis revealed elevation of total bile acids, bilirubin and transaminases. Based on the clinical characteristics and the consultation opinion of the ophthalmologist, the child was diagnosed to have ALGS with Duane retraction syndrome. DNA direct sequencing detected a novel JAG1 mutation c.2419delG(p.Glu807AsnfsX819) in the child. Symptomatic and supportive therapy was performed thereafter and clinical follow-up was conducted until he was 4 years and 2 months. In the follow-up visits, his general condition remained stable, but the facial malformations, left esotropia, cardiac murmur and abnormal liver function persistend. The long-term outcome needed to be observed.
Alagille Syndrome ; genetics ; therapy ; Child, Preschool ; Humans ; Jagged-1 Protein ; genetics ; Male ; Mutation

9.Clinical and genetic study of an infant with Alagille syndrome: identification of a novel chromosomal interstitial deletion including JAG1 gene.

Hua LI ; Jia-Jia LIU ; Mei DENG ; Li GUO ; Ying CHENG ; Yuan-Zong SONG

Chinese Journal of Contemporary Pediatrics 2017;19(10):1098-1103

Alagille syndrome (ALGS) is an autosomal dominant disease affecting multiple systems including the liver, heart, skeleton, eyes, kidneys and face. This paper reports the clinical and genetic features of an infant with this disease. A 3-month-and-10-day-old female infant was referred to the hospital with jaundiced skin and sclera for 3 months. Physical examination revealed wide forehead and micromandible. A systolic murmur of grade 3-4/6 was heard between the 2th and 3th intercostal spaces on the left side of the sternum. The abdomen was distended, and the liver palpable 3 cm under the right subcostal margin with a medium texture. Serum biochemistry analysis revealed abnormal liver function indices, with markedly elevated bilirubin (predominantly direct bilirubin), total bile acids (TBA) and gamma-glutamyl transpeptidase (GGT). Atrial septal defect and pulmonary stenosis were detected on echocardiography. Next generation sequencing detected entire deletion of the JAG1 gene, and then chromosomal microarray analysis revealed a novel interstitial deletion of 3.0 Mb in size on chr20p12.3p12.2, involving JAG1 gene. The child had special facial features, heart malformations, and cholestasis, and based on the genetic findings, ALGS was definitively diagnosed. Thereafter, symptomatic and supportive treatment was introduced. Thus far, the infant had been followed up till his age of 11 months. The hyperbilirubinemia got improved, but GGT and TBA were persistently elevated, and the long-term outcome needs to be observed. This study extended the JAG1 mutation spectrum, and provided laboratory evidences for the diagnosis and treatment of the patient, and for the genetic counseling and prenatal diagnosis in the family.
Alagille Syndrome ; genetics ; Bile Acids and Salts ; blood ; Child, Preschool ; Chromosome Deletion ; Humans ; Jagged-1 Protein ; genetics ; Male ; gamma-Glutamyltransferase ; blood