Neonatal cholestasis
Gene: CLDN1Comment 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.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
ichthyosis-hypotrichosis-sclerosing cholangitis
Variants in this GENE are reported as part of current diagnostic practice
This panel has been subjected to extensive internal and external review.
Gene: cldn1 has been classified as Green List (High Evidence).
Gene: cldn1 has been classified as Green List (High Evidence).
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
Publications for gene: CLDN1 were set to 12164927; 15521008; 24641442; 28154377; 16619213; 29146216
Phenotypes for gene: CLDN1 were set to Neonatal and Adult Cholestasis; Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis, 607626; ichthyosis-hypotrichosis-sclerosing cholangitis
Publications for gene: CLDN1 were set to 12164927; 15521008
Mode of inheritance for gene: CLDN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene CLDN1 were set to Neonatal and Adult Cholestasis, Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis, 607626
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
Victorian Clinical Genetics Services was added to CLDN1. Panel: Cholestasis
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
CLDN1 was added to Cholestasis panel. Sources: Emory Genetics Laboratory
CLDN1 was created by Ellen McDonagh