Two Novel Mutations in the JAG1 Gene in Pediatric Patients with Alagille Syndrome: The First Case Series in Czech Republic

被引:2
作者
Prochazkova, Dagmar [1 ,2 ]
Borska, Romana [3 ]
Fajkusova, Lenka [3 ]
Konecna, Petra [1 ]
Hlouskova, Eliska [1 ]
Pavlovsky, Zdenek [4 ]
Slaby, Ondrej [5 ,6 ]
Pospisilova, Sarka [2 ,3 ,6 ]
机构
[1] Masaryk Univ, Univ Hosp Brno, Dept Pediat, Fac Med, Brno 62500, Czech Republic
[2] Masaryk Univ, Univ Hosp Brno, Dept Clin Genet & Genom, Fac Med, Brno 62500, Czech Republic
[3] Masaryk Univ, Univ Hosp Brno, Dept Internal Med, Ctr Mol Biol & Genet, Brno 62500, Czech Republic
[4] Masaryk Univ, Univ Hosp Brno, Dept Pathol, Fac Med, Brno 62500, Czech Republic
[5] Masaryk Univ, Dept Biol, Fac Med, Brno 62500, Czech Republic
[6] Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic
关键词
Alagille syndrome; JAG1; gene; pediatric patients; cholestasis; NOTCH2; MUTATIONS; HUMAN JAGGED1; SPECTRUM;
D O I
10.3390/diagnostics11060983
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Alagille syndrome (ALGS) is a highly variable multisystem disorder inherited in an autosomal dominant pattern with incomplete penetration. The disorder is caused by mutations in the JAG1 gene, only rarely in the NOTCH2 gene, which gives rise to malformations in multiple organs. Bile duct paucity is the main characteristic feature of the disease. Methods: Molecular-genetic examination of genes JAG1 and NOTCH2 in four probands of Czech origin who complied with the diagnostic criteria of ALGS was performed using targeted next-generation sequencing of genes JAG1 and NOTCH2. Segregation of variants in a family was assessed by Sanger sequencing of parental DNA. Results: Mutations in the JAG1 gene were confirmed in all four probands. We identified two novel mutations: c.3189dupG and c.1913delG. Only in one case, the identified JAG1 mutation was de novo. None of the parents carrying JAG1 pathogenic mutation was diagnosed with ALGS. Conclusion: Diagnosis of the ALGS is complicated due to the absence of clear genotype-phenotype correlations and the extreme phenotypic variability in the patients even within the same family. This fact is of particular importance in connection to genetic counselling and prenatal genetic testing.
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页数:7
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