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We identified novel biallelic mutations in the DCDC2 gene causing neonatal sclerosing cholangitis (NSC) in a Chinese family. Up to date, only five DCDC2 variants associated with NSC have been entered HGMD. Our study expanded the mutational spectrum of DCDC2. We also suggest that those patients who with a presumptive diagnosis of NSC need to pay more attention to DCDC2 and CLDN1 genes.
Neonatal sclerosing cholangitis (NSC) is a severe cholestatic liver disease, which often develops into end-stage liver disease in childhood and requires liver transplantation. Mutations in CLDN1 and DCDC2 are confirmed to be the main pathogenic mechanism of NSC.
Whole exon sequencing (WES) was performed to find the possible disease-causing mutations of this family. The mutation was confirmed by Sanger sequencing, and large fragment copy number variation was confirmed by qPCR.
We found novel biallelic mutations c.[705-2A>G];[923_1023del] in the DCDC2 gene of the proband. The proband's father had the heterozygous mutation c.705-2A>G, and his mother had a heterozygous c.923_1023del. The proband's younger brother, who had similar clinical manifestations, was found the same biallelic mutations with the proband.
Novel biallelic mutations were identified in DCDC2 of this Chinese family, according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants, both mutations were classified as pathogenic, which might be the cause of NSC in this family.Le texte complet de cet article est disponible en PDF.
Keywords : Neonatal sclerosing cholangitis, Doublecortin domain-containing protein 2, Biallelic mutations, Whole exon sequencing, Copy number variation