Neonatal cholestasis

Gene: CLDN1

Green List (high evidence)

CLDN1 (claudin 1)
EnsemblGeneIds (GRCh38): ENSG00000163347
EnsemblGeneIds (GRCh37): ENSG00000163347
OMIM: 603718, Gene2Phenotype
CLDN1 is in 6 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as Ready, July 25th. Sufficient evidence (>3 unrelated cases and expert review) for Green rating.
Created: 25 Jul 2018, 10:43 a.m.
Comment on list classification: Updated rating from Amber to Green following curator review. Green expert review and used in diagnosis, PLUS >3 unrelated cases (and >3 variants) from OMIM and literature of CLDN1 variants causing sclerosing cholangitis, a progressive cholestatic liver disease.
Created: 25 Jul 2018, 10:42 a.m.
2 unrelated cases of sclerosing cholangitis (MIM:607626) with 2 variants featured on MIM from PMID:15521008 (2004) and PMID:16619213 (2006). Further cases with additional variants reported in more recent literature: PMID:28154377 (2017) present a consanguineous family with NISCH syndrome and a homozygous p.Tyr159Ter mutation in the patients. PMID:24641442 (2014) report 2 patients from a Turkish family with NISCH syndrome and a homozygous variant in CLDN1 (c.181C>T, p.Gln61X).
Created: 25 Jul 2018, 10:39 a.m.
Comment on mode of inheritance: Biallelic MOI confirmed by OMIM.
Created: 25 Jul 2018, 9:43 a.m.

Jane Hartley (Birmingham Women and Children's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ichthyosis-hypotrichosis-sclerosing cholangitis

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
Phenotypes
  • Neonatal and Adult Cholestasis
  • Ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis, 607626
  • ichthyosis-hypotrichosis-sclerosing cholangitis
  • NISCH syndrome
  • Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome
OMIM
603718
Clinvar variants
Variants in CLDN1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Sep 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been subjected to extensive internal and external review.

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: cldn1 has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: cldn1 has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: CLDN1 were set to Neonatal and Adult Cholestasis; Ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis, 607626; ichthyosis-hypotrichosis-sclerosing cholangitis; NISCH syndrome; Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome

25 Jul 2018, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: CLDN1 were set to 12164927; 15521008; 24641442; 28154377; 16619213; 29146216

25 Jul 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: CLDN1 were set to Neonatal and Adult Cholestasis; Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis, 607626; ichthyosis-hypotrichosis-sclerosing cholangitis

25 Jul 2018, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: CLDN1 were set to 12164927; 15521008

25 Jul 2018, Gel status: 2

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: CLDN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

25 Jul 2018, Gel status: 2

Set penetrance

Rebecca Foulger (Genomics England curator)

Phenotypes for gene CLDN1 were set to Neonatal and Adult Cholestasis, Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis, 607626

25 Jul 2018, Gel status: 2

Removed Source, Set penetrance

Rebecca Foulger (Genomics England curator)

Source Victorian Clinical Genetics Services was removed from CLDN1. Panel: Cholestasis Phenotypes for gene CLDN1 were set to Neonatal and Adult Cholestasis, Ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis, Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis, 607626

21 Jun 2018, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Victorian Clinical Genetics Services was added to CLDN1. Panel: Cholestasis

18 May 2018, Gel status: 2

Added New Source, Set mode of inheritance, Set penetrance

Ellen McDonagh (Genomics England Curator)

UKGTN was added to CLDN1. Panel: Cholestasis Model of inheritance for gene CLDN1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene CLDN1 were set to Neonatal and Adult Cholestasis, Ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis

18 May 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CLDN1 was added to Cholestasis panel. Sources: Emory Genetics Laboratory

18 May 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

CLDN1 was created by Ellen McDonagh