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Until now, only one case of profound T-cell immune deficiency with complete LCK deficiency [1] caused by a biallelic missense mutation (c.1022T&gt;C, p.L341P) and three cases of incomplete LCK deficiency [2] caused by a biallelic splice site mutation (c.188-2A&gt;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 <jats:italic>LCK<\/jats:italic> (c.1393T&gt;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<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> \u03b1\u03b2T-cells and homeostatic T-cell expansion was accompanied by increased \u03b3\u03b4T-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.<\/jats:p>","DOI":"10.1007\/s10875-023-01602-8","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T09:02:22Z","timestamp":1702630942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature"],"prefix":"10.1007","volume":"44","author":[{"given":"Anna-Lisa","family":"Lanz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serife","family":"Erdem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alper","family":"Ozcan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulay","family":"Ceylaner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"Cansever","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar","family":"Ceylaner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"Conca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Magg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oreste","family":"Acuto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Latour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turkan","family":"Patiroglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekrem","family":"Unal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"Eken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Hauck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"issue":"5","key":"1602_CR1","doi-asserted-by":"publisher","first-page":"1144-52 e11","DOI":"10.1016\/j.jaci.2012.07.029","volume":"130","author":"F Hauck","year":"2012","unstructured":"Hauck F, Randriamampita C, Martin E, Gerart S, Lambert N, Lim A, et al. 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