CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review
Abstract
:1. Introduction
2. Subjects and Methods
2.1. Clinical Phenotype
2.2. Genetic Analysis and In Silico Predictions
3. Results
3.1. Genetic Findings
3.2. Phenotypic Constellation in CTLA4 c.436G>A Carriers
4. Discussion
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study (PMID) | Immunological | Gastrointestinal | Respiratory | Neurological | Hematological | Skin | Endocrine | Skeletal | Others |
---|---|---|---|---|---|---|---|---|---|
29729943 (Individual #53, fam V.II.1) | Lymphadenopathy | Lymphocytic organ infiltration (retroperitoneum) | ITP; AIHA; autoimmune neutropenia; Evans syndrome | Renal involvement | |||||
29729943 (Individual #99, fam SS.II.1) | Hypogammaglobulinemia (low IgG, IgM, IgA); fungal infections (Candida) | Splenomegaly; diarrhea/enteropathy, atrophic gastritis | Respiratory involvement, (upper and lower respiratory tract); severe respiratory infections (pneumonia); GLILD; bronchiectasis; lymphadenopathy and lymphocytic organ infiltration (lungs) | Lymphadenopathy and lymphocytic organ infiltration (brain); retinal tear due to lymphocytic infiltrations into the retina | RA | ||||
28960754 | Autoimmune lymphoproliferative syndrome (ALPS) | Hepatomegaly; splenomegaly | Evans syndrome | ||||||
31993940 | Positivity for anti-parietal cell antibody; hypogammaglobulinemia (low IgG) | Recurrent diarrhea; atrophic gastritis; lymphoid hyperplasia at the ileal end | Recurrent respiratory infection | Dysphagia since age 3 years | IDA; ITP; leukopenia; | Bilateral axillary lymphadenopathy | Cervical lymphadenopathy; bilateral knee arthralgia; steroid refractory RA | ||
32996901 | Reduction of CD19+ B cells, low levels of total IgG and IgA, and a normal IgE level; CMV infection; reduced PBMC count | Chronic diarrhea; enteropathy; cholecystectomy (probably due to AIHA) | Chronic sinusitis | ITP; Evans syndrome | Alopecia areata | Hypothyroidism, diabetes mellitus type 1 | |||
35753512 (P0003698) | Chronic infections; fever | Abdominal pain; splenomegaly; diarrhea | Abnormal lung morphology; pulmonary obstruction | Abnormality of vision; nausea; vomiting; anxiety; seizures; abdominal pain; distal muscle weakness; headache | AIHA; IDA | Urticaria; blepharitis | Weight loss | ||
32623363 | Hypogammaglobulinemia; polyvalent allergy | Crohn’s disease; sphincter dysfunction (bowel) | Bilateral pulmonary interstitial infiltration; chronic pansinusitis | Progressive headache and focal right-side-sensitive epileptic paroxysm; presence of an isolated infiltrating mass (16 × 20 × 22 mm) and lesions in the white-matter (left parieto-occipital region); T2-hyperintense lesion in the right counterpart; positive sensory symptoms in both hands; static tremor and hypesthesia of the left upper extremity (suspected MS); idiopathic intracranial hypertension; moderate central paraparesis of the lower extremities; hypesthesia; disseminated intramedullary lesions; CSF oligoclonal bands | Autoimmune thyroiditis | Juvenile seronegative RA | Recurrent uveitis, with permanent moderate vision loss due to papilledema; sphincter dysfunction (bladder) | ||
31955317 | Immunodeficiency with low IgG and undetectable IgA and IgM levels; CD19+ B cells were absent; lower count of CD4+ T cells; elevated lactate dehydrogenase level | Cholestasis; mediastinal adenopathy; hepato-splenomegaly, multiple lytic lesions of the liver | Interstitial fibrosis of the left lung with focal honeycombing and lymphocytes infiltrates in the fibrotic areas; sinopulmonary infections; progressive respiratory distress with hypoxemia; dyspnea | ITP progressed to pancytopenia with lymphopenia by age 23 years; erythroid and megakaryocytic hyperplasia | Anasarca; axillary lymphadenopathy | Multiple lytic lesions in the skull, ribs, and spine; cervical lymphadenopathy | |||
36790564 | Unspecified primary B cell defects | ||||||||
30443250 | Immune dysregulation-IPEX | ||||||||
Current study | Immunodeficiency; hypogammaglobulinemia (low IgG, IgA, IgM, IgE); CVID | Chronic diarrhea; enteropathy; gallstones; celiac disease/IBD; poliposis | Interstitial pneumopathy | Hypodensity in the pons region; vermis lesions; hydrocephalus; seizures; CNS demyelination | Autoimmune thrombocytopenia; hemolytic anemia | Psoriasiform dermatitis (father) | Hashimoto thyroiditis (father and cousin) | Osteoporosis; RA (niece) | Growth delay |
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Genio, E.; Lecca, M.; Ciccocioppo, R.; Errichiello, E. CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review. Genes 2025, 16, 306. https://doi.org/10.3390/genes16030306
Genio E, Lecca M, Ciccocioppo R, Errichiello E. CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review. Genes. 2025; 16(3):306. https://doi.org/10.3390/genes16030306
Chicago/Turabian StyleGenio, Edoardo, Mauro Lecca, Rachele Ciccocioppo, and Edoardo Errichiello. 2025. "CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review" Genes 16, no. 3: 306. https://doi.org/10.3390/genes16030306
APA StyleGenio, E., Lecca, M., Ciccocioppo, R., & Errichiello, E. (2025). CTLA4 Alteration and Neurologic Manifestations: A New Family with Large Phenotypic Variability and Literature Review. Genes, 16(3), 306. https://doi.org/10.3390/genes16030306