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- Title
JAG1 MUTATION SPECTRUM IN CASES WITH ALAGILLE SYNDROME FROM TURKIYE.
- Authors
ASLANGER, Ayça Dilruba; YILDIRIM, Behiye Tuğçe; KALAYCI, Tuğba; ŞENTÜRK, Leyli; AVCI, Şahin; ALTUNOĞLU, Umut; GÜLEÇ, Çağrı; KARAMAN, Volkan; DOĞAN, Güzide; ÖNAL, Zerrin; DURMAZ, Özlem; KARAMAN, Birsen; UYGUNER, Zehra Oya
- Abstract
Objective: Alagille syndrome (ALGS), known as arteriohepatic dysplasia, is an autosomal dominant multisystem disorder primarily linked to JAG1 gene variants. It features distinctive anomalies in the liver, heart, eyes, spine, and facial morphology. Material and Method: Patients diagnosed with ALGS and referred to Istanbul Faculty of Medicine, Department of Medical Genetics between January 2016 and December 2022 were included in the study. The clinical, radiological, cytogenetic, and molecular findings of the patients as well as their families were re-assessed retrospectively. Karyotype, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and JAG1 gene sequencing utilizing next-generation and Sanger sequencing methodologies were conducted. Result: The presence of both large deletion and small variants associated with Alagille syndrome was detected in all cases. In karyotype and aCGH analysis of a single case, a 20p deletion was identified. Subsequent next-generation sequencing (NGS) of the JAG1 gene revealed the following findings: a heterozygous pathogenic variant c.2122_2125del/p.(Gln708Valfs*34), a heterozygous likely pathogenic variant c.1754_1755del/p.(Asn585Argfs*4), a heterozygous pathogenic variant c.2026del/p.(Cys676Alafs*67), a heterozygous pathogenic variant c.753C>A/p.(Cys251*), and a heterozygous likely pathogenic variant c.2458+2_2458+4delTAAinsGAC/p. (?). In one case, FISH analysis revealed a 20p deletion inherited from the mother. Analysis of available family members further indicated that three variants were inherited within the family. One of the two novel truncating variants, the c.1754_1755del variant was identified as de novo, while the other c.2458+2_2458+4delTAAinsGAC variant was determined to be familial. Conclusion: In summary, the research effectively identified various JAG1 gene alterations and underlined the significance of incorporating molecular cytogenetic analysis in conjunction with sequence analysis of the JAG1 gene for accurate genetic diagnosis and counseling. Furthermore, study highlights the valuable outcome of screening parents, siblings, and children to clarify the genetic etiopathogenesis, as there is a remarkable intra- and inter-familial phenotypic variability in patients with ALGS.
- Subjects
GENETIC variation; MEDICAL genetics; COMPARATIVE genomic hybridization; FLUORESCENCE in situ hybridization; NUCLEOTIDE sequencing
- Publication
Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi, 2023, Vol 86, Issue 4, p327
- ISSN
1305-6441
- Publication type
Article
- DOI
10.26650/IUITFD.1321220