Co-existence of ABCB11 and DCDC2 disease: Infantile cholestasis requires both next-generation sequencing and clinical-histopathologic correlation

Vogel, Georg-Friedrich; Maurer, Elisabeth; Entenmann, Andreas; Straub, Simon; Knisely, A. S.; Janecke, Andreas R.; Müller, Thomas

doi:10.1038/s41431-020-0613-0

Cited by 5 publications

(13 citation statements)

References 17 publications

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“…Biallelic pathogenic variants in DCDC2 are a known cause for NSC, nephronophthisis, and deafness 2,3,5,10–13 . We now report two unrelated patients with homozygous pathogenic variants in DCDC2 , presenting with NSC, developmental delay, and microcephaly, and excluded other known genetic causes for intellectual disability (suppl.…”

Section: Discussionmentioning

confidence: 84%

Two cases of DCDC2‐related neonatal sclerosing cholangitis with developmental delay and literature review

et al. 2021

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Ciliopathies are a group of clinical and molecular heterogeneous conditions with pleiotropic manifestations affecting the central nervous system, renal, liver, skeletal, and ocular systems. Biallelic pathogenic variants in DCDC2 cause a ciliopathy primarily presenting with neonatal sclerosing cholangitis (NSC). Pathogenic variants in DCDC2 have further been reported in the context of nephronophthisis and non‐syndromic recessive deafness. Polymorphisms in DCDC2 have also been associated with dyslexia and DCDC2 has a role in neuronal development. We report on two unrelated patients with DCDC2‐related NSC with additional central nervous system impairment manifesting as microcephaly, global developmental delay, and axial hypotonia. Histological findings of our patients can mimic biliary atresia or congenital hepatic fibrosis. We further show that transmission electron microscopy in patients with NSC does not always show absence of primary cilia. Hence patients with DCDC2 pathogenic variants should also undergo an evaluation of neuromotor development. Review of all reported patients further reveals a risk for supra‐aortic arterial aneurysms.

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Section: Discussionmentioning

confidence: 84%

Two cases of DCDC2‐related neonatal sclerosing cholangitis with developmental delay and literature review

et al. 2021

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“…With the development of whole-exome sequencing (WES), more and more DCDC2 mutations have been identified. To our knowledge, seventeen cases of NSC caused by DCDC2 mutation with 12 variants have been reported worldwide (4,6,(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Neonatal sclerosing cholangitis with novel mutations in DCDC2 (doublecortin domain-containing protein 2) in Chinese children

et al. 2023

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BackgroundNeonatal sclerosing cholangitis (NSC) is a rare and severe autosomal recessive inherited liver disease with mutations in DCDC2, commonly requiring liver transplantation (LT) for decompensated biliary cirrhosis in childhood.MethodsThe information of four Chinese patients with NSC caused by mutations in DCDC2 from Children's Hospital of Fudan University were gathered. The four patients' clinicopathological and molecular features were summarized by clinical data, liver biopsy, immunohistochemical, and molecular genetic analysis.ResultsAll patients presented with jaundice, hepatosplenomegaly, hyperbilirubinemia and bile embolism, and high serum γ-glutamyl transferase activity (GGT). Liver biopsies revealed varying degrees of bile duct hyperplasia, portal-tract inflammation, and/or fibrosis. Whole-exome sequencing (WES) found novel heterozygous variants of c.1024-1G > T /p.? and c.544G > A /p. Gly182Arg in the DCDC2.ConclusionThis study expands the genetic spectrum of DCDC2 in NSC.

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“…Neonatal sclerosing cholangitis (NSC) mimics extrahepatic biliary atresia both clinically, with conjugated hyperbilirubinemia and high serum gamma-glutamyl transpeptidase activity (GGT), and histopathologically, with portal-tract bile plugging, ductular proliferation and fibrosis on liver biopsy. [1][2][3] In contrast to biliary atresia, the biliary tract is patent, albeit strictured, in NSC. Genes implicated in NSC include CLDN1 (MIM *603718), encoding claudin-1, 4 ZFYVE19 (MIM *619635), encoding zinc finger FYVE-type containing 19, 5 and DCDC2 (MIM *605755), encoding doublecortin domain-containing 2.…”

Section: Introductionmentioning

confidence: 99%

“…The structural hallmark of DCDC2-associated liver disease is the ductal plate malformation (DPM), seen in many ciliopathic disorders. 2,3 Variants in DCDC2 are also associated with sclerosing cholangiopathy, deafness, dyslexia, developmental delay and nephronophthisis (MIM #617394, #610212, #616217). [1][2][3][6][7][8][9][10][11] Here we present four patients with either novel homozygous variants or compound heterozygous variants in DCDC2 of whom three had NSC and one had a cholangiopathy manifest only as a toddler.…”

Section: Introductionmentioning

confidence: 99%

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Biallelic known and novel DCDC2 variants in cholestatic liver disease: Phenotype–genotype observations in four children

Azabdaftari

Sczakiel

Danyel

et al. 2023

Liver International

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Neonatal sclerosing cholangitis (NSC) is associated with progressing biliary fibrosis that often requires liver transplantation in childhood. Several recent studies have identified variants in DCDC2, encoding doublecortin domain-containing protein 2 (DCDC2), expressed in primary cilia, that accompany syndromic disease and NSC. We report four patients with hepatobiliary disease associated with two novel homozygous or compound heterozygous variants in DCDC2. Three patients with protein-truncating variants in DCDC2, expressing no DCDC2, presented with the originally described severe hepatic phenotype in infancy. One patient with a novel homozygous DCDC2 missense variant shows a markedly milder phenotype only manifest in childhood and with retained DCDC2 expression. Concomitant nephronophthisis is present in three patients and learning disability in two. This report widens the phenotypic spectrum of DCDC2-associated hepatobiliary disease. Testing for DCDC2 expression and DCDC2 variants should be included in the evaluation of cholangiopathy of unknown aetiology in childhood as well as in infancy.

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Co-existence of ABCB11 and DCDC2 disease: Infantile cholestasis requires both next-generation sequencing and clinical-histopathologic correlation

Cited by 5 publications

References 17 publications

Two cases of DCDC2‐related neonatal sclerosing cholangitis with developmental delay and literature review

Two cases of DCDC2‐related neonatal sclerosing cholangitis with developmental delay and literature review

Neonatal sclerosing cholangitis with novel mutations in DCDC2 (doublecortin domain-containing protein 2) in Chinese children

Biallelic known and novel DCDC2 variants in cholestatic liver disease: Phenotype–genotype observations in four children

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