Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PTCRA

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:34 p.m. | Last Modified: 26 Sep 2024, 3:34 p.m.

Panel Version: 6.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

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

• 38422122

Green List (high evidence)

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: Literature

Created: 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

• 38422122