Nephronophthisis due to a novel <i>DCDC2</i> variant in a patient from African‐Caribbean descent: A case report

Slater, Brady; Bekheirnia, Nasim; Angelo, Joseph; Bi, Weimen; Braun, Michael C.; Bekheirnia, Mir Reza

doi:10.1002/ajmg.a.61440

Cited by 4 publications

(6 citation statements)

References 8 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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“…A total number of 28 patients (from 24 families) affected with DCDC2-related ciliopathy were identified [8][9][10][11][12][13][14][15][16][17]. A detailed clinical, biochemical, pathological and molecular characterisation was provided in Table 3.…”

Section: Literature Reviewmentioning

confidence: 99%

DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases

Lipiński,

Ciara,

Jurkiewicz

et al. 2023

Diagnostics

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Introduction: The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the DCDC2 gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with DCDC2 biallelic pathogenic variants. A detailed overview of the reported patients with DCDC2-related disease was provided. Material and methods: A retrospective chart review of the clinical, biochemical, pathological (liver histology) and molecular features of the study group was performed. The database PubMed (MEDLINE) was searched for relevant studies. Results: All the patients presented with cholestatic jaundice and elevated GGT; the mean age was 2 months. The initial liver biopsy was performed in four children at a mean age of 3 months (age range: 2–5 months). In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. Only one patient presented with features of renal disease. Whole exome sequencing was performed in all patients at the last follow-up visit (mean age 10 years). Three different variants (one novel) in the DCDC2 gene were identified in the study group. With our six patients, a total of 34 patients with DCDC2-related hepatic ciliopathy were identified. The main clinical presentation of DCDC2-related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. The predominance of early and severe liver disease associated with no or mildly expressed kidney involvement was observed. Conclusions: Our findings expand the molecular spectrum of pathogenic DCDC2 variants, provide a more accurate picture of the phenotypic expression associated with molecular changes in this gene and confirm a loss of functional behaviour as the mechanism of disease.

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“…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. Syndromic features of the disease included nephronophthisis.…”

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) 1–3,6–11 …”

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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Nephronophthisis due to a novel DCDC2 variant in a patient from African‐Caribbean descent: A case report

Cited by 4 publications

References 8 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

DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases

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

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