Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: PTCRA
Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.Created: 17 Apr 2024, 5:50 p.m. | Last Modified: 17 Apr 2024, 5:50 p.m.
Panel Version: 4.201
As reviewed by Boaz Palterer, PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds).
Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons.
Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available.
This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.Created: 17 Apr 2024, 5:49 p.m. | Last Modified: 17 Apr 2024, 5:49 p.m.
Panel Version: 4.199
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Publications
Materna et al. identified 10 subjects from 7 kindreds with biallelic LOF PTCRA variants, moreover, the authors identified common hypomorphic alleles significantly associated with autoimmunity. Extensive in vivo, in vitro, and mouse functional validation and epidemiologic data.
Sources: LiteratureCreated: 10 Mar 2024, 12:20 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC
Publications
Gene: ptcra has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PTCRA were changed from Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Tag Q2_24_promote_green tag was added to gene: PTCRA.
gene: PTCRA was added gene: PTCRA was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCRA were set to 38422122 Phenotypes for gene: PTCRA were set to Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC Penetrance for gene: PTCRA were set to Incomplete Review for gene: PTCRA was set to GREEN