Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TERC

I don't know

Agree immune deficiency is not a predominant feature

Created: 29 Jun 2018, 3:31 p.m.

Comment on list classification: Rating gene as amber after review from Genomics England clinical team. Lack of PID phenotype in the majority of individuals.

Created: 19 Jun 2018, 9:10 a.m.

Asked for Genomics England clinical team input as to whether this gene should be rated green, even though there are enough cases, since there is incomplete penetrance and variable clinical phenotypes relating to immunodeficiency.

Created: 14 Jun 2018, 12:08 p.m.

Comment on publications: Added publications

Created: 14 Jun 2018, 10:04 a.m.

In OMIM this gene is associated with Dyskeratosis congenita, autosomal dominant 1. A severe form of this disorder is Hoyeraal-Hreidarsson syndrome which is characterised by a number of phenotypes including bone marrow failure resulting in immunodeficiency. However, asymptomatic individuals with only mild hematologic abnormalities have been observed in families with the autosomal dominant form of DC (Vulliamy et al 2006 (PMID: 16332973). OMIM reports that Vulliamy et al. (2001) (PMID:11574891) identified 3 different mutations in TERC in 3 families segregating autosomal dominant dyskeratosis congenita-1; a 821-bp deletion including the 74 3-prime basepairs of the coding region, a SNV and a 2 bp substitution. The first deletion results in barely detectable transcript levels. The other two are thought to destabilise the protein (Thiemer et al 2003, PMID: 12525685). Vulliamy et al 2006 (PMID: 16332973) report a further 3 variants in TERC in patients with autosomal dominant Dyskeratosis congenita (a 1 bp and a 4 bp deletion, and a 1 bp substitution). They also note that there is disease anticipation in families with asymptomatic parent being shown to carry the TERC mutation.

Created: 14 Jun 2018, 9:57 a.m.

I don't know

added locus-type-rna-misc tag

Created: 9 Jul 2018, 8:46 a.m.

Keep Amber until more info on gene and disease association, immune deficiency is not a predominant feature in the majority of individuals

Created: 5 Jul 2018, 1:20 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TERC .PanelApp HGNC gene symbol check: TERC . IUIS Disease: AD-DKC due to TERC deficiency . IUIS Inheritance: AD .T cells: N/A, .B cells: Variable, .IUIS Other affected cells: N/A. IUIS Associated features: Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DyskeratosIs Congenita (DKC), Myelodysplasia, Short Telomeres

Created: 2 Jul 2018, 10:35 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 19 Apr 2018, 1:15 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: TERC, PanelApp HGNC gene symbol check: TERC, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Dyskeratosis congenita / Dyskeratosis congenita; Other well defined PIDs / Dyskeratosis congenita / Hoyeraal-Hreidarsson syndrome

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TERC, GRID_Gene_Symbol: TERC, GRID_Transcript_ENS_Community submitted: ENST00000602385, GRID_Transcript_RefSeq: NR_001566.1, GRID_Transcript_ENS_used_on_Production: ENST00000602385

Created: 17 Apr 2018, 12:12 p.m.