CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review

Case#: III:3, female, 45 years old, Italian

DiseaseAssertion: Celiac disease/IBD with immunodeficiency (CVID) and CNS demyelination

FamilyInfo: non-consanguineous Italian parents, history of autoimmune disorders (Hashimoto thyroiditis, psoriasiform dermatitis, celiac disease and rheumatoid arthritis), see Figure 1 CasePresentingHPOs: HP:0002028, HP:0002721, HPO:0001888, HPO:0008897, HP000:6515, HP:0002110, HP:0011108, HP:0001878, HP:0001973, HP:0031688, HP:0007185, HP:0002140, HP:0001081, HP:0011097, HP:0001945, HP:0007305, HP:0000238, HP:0200063, HP:0004313, HP:0000939, HP:0030252

CasePreviousTesting: whole-exome sequencing on the proband and parental DNA samples (trio-WES) from peripheral blood

GenotypingMethod: Reads aligned against GRCh38/hg38, variant calling using in-house pipeline according to international guidelines, variants with a frequency of <5% in gnomAD v4.1.0 and an in-house database, virtual panel of 564 genes related to primary immunodeficiency and inflammatory bowel disease (PanelApp version 7.21), CNVs detected with Control-FREEC and EXCAVATOR tools

**Variant: ** NM_005214.5:c.436G>A; p.Gly146Arg

ClinVar: VCV000849622.11

gnomAD: 0.000001696 https://gnomad.broadinstitute.org/variant/2-203870912-G-A?dataset=gnomad_r4

Liu, Y., Ebinger, J. E., Mostafa, R., Budde, P., Gajewski, J., Walker, B., Joung, S., Wu, M., Bräutigam, M., Hesping, F., Rupieper, E., Schubert, A.-S., Zucht, H.-D., Braun, J., Melmed, G. Y., Sobhani, K., Arditi, M., Van Eyk, J. E., Cheng, S., & Fert-Bober, J. (2021). Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection. Journal of Translational Medicine, 19(1), 524. https://doi.org/10.1186/s12967-021-03184-8

Greinacher, A., Thiele, T., Warkentin, T. E., Weisser, K., Kyrle, P. A., & Eichinger, S. (2021). Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. New England Journal of Medicine, 384(22), 2092–2101. https://doi.org/10.1056/NEJMoa2104840

Pishko, A. M., Bussel, J. B., & Cines, D. B. (2021). COVID-19 vaccination and immune thrombocytopenia. Nature Medicine, 1–2. https://doi.org/10.1038/s41591-021-01419-1

Mandavilli, A. (2021, January 28). Some Covid Survivors Have Antibodies That Attack the Body, not Virus. The New York Times. https://www.nytimes.com/2020/10/27/health/covid-antibodies-autoimmunity.html

LNP and PEG can cause autoimmune disease. They also damage the liver.

Mannix, L. (2021, February 8). Where did these COVID-19 variants come from – and what are they? The Sydney Morning Herald. https://www.smh.com.au/national/what-do-new-variants-of-the-coronavirus-mean-for-us-20210126-p56wuo.html

That's a lot of people too.

That's a lot of people.

This is interesting. Relates to this other research.