A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature
Yazarlar (15)
Dr. Öğr. Üyesi Şerife ERDEM Türkiye
Anna-Lısa Lanz
Türkiye
Türkiye
Alper Özcan Erciyes Üniversitesi, Türkiye
Gülay Ceylaner Türkiye
Murat Cansever
Türkiye
Türkiye
Serdar Ceylaner Türkiye
Raffaele Conca
Thomas Magg
Oreste Acuto
Sylvain Latour
Christoph Klein
Türkan Patıroğlu
Türkiye
Türkiye
Ekrem Ünal Türkiye
Ahmet Eken Erciyes Üniversitesi, Türkiye
Fabian Hauck
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | Springer Science and Business Media LLC (Q1) | ||
| Dergi ISSN | 0271-9142 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 12-2023 |
| Cilt / Sayı / Sayfa | 44 / 1 / – | DOI | 10.1007/s10875-023-01602-8 |
| Makale Linki | http://dx.doi.org/10.1007/s10875-023-01602-8 | ||
| Özet |
| Lymphocyte-specific protein tyrosine kinase (LCK) is an SRC-family kinase critical for initiation and propagation of T-cell antigen receptor (TCR) signaling through phosphorylation of TCR-associated CD3 chains and recruited downstream molecules. Until now, only one case of profound T-cell immune deficiency with complete LCK deficiency [1] caused by a biallelic missense mutation (c.1022T>C, p.L341P) and three cases of incomplete LCK deficiency [2] caused by a biallelic splice site mutation (c.188-2A>G) have been described. Additionally, deregulated LCK expression has been associated with genetically undefined immune deficiencies and hematological malignancies. Here, we describe the second case of complete LCK deficiency in a 6-month-old girl born to consanguineous parents presenting with profound T-cell immune deficiency. Whole exome sequencing (WES) revealed a novel pathogenic biallelic missense mutation in LCK (c.1393T>C, p.C465R), which led to the absence of LCK protein expression and phosphorylation, and a consecutive decrease in proximal TCR signaling. Loss of conventional CD4 and CD8 αβT-cells and homeostatic T-cell expansion was accompanied by increased γδT-cell and Treg percentages. Surface CD4 and CD8 co-receptor expression was reduced in the patient T-cells, while the heterozygous mother had impaired CD4 and CD8 surface expression to a lesser extent. We conclude that complete LCK deficiency is characterized by profound T-cell immune deficiency, reduced CD4 and CD8 surface expression, and a characteristic TCR signaling disorder. CD4 and CD8 surface expression may be of value for early detection of mono- and/or biallelic LCK deficiency. |
| Anahtar Kelimeler |
| LCK deficiency | inborn errors of immunity | profound T-cell immune deficiency | TCR signaling | CD4 and CD8 co-receptor expression |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 13 |