PMC9626757_01
The timeline of case report.
fimmu-13-1033338-g001.jpg
PMC9626757_06_fimmu-13-1033338-g001.jpg
f1
The patient developed mixed hematopoietic chimerism that stabilized at the level of 60-70% mononuclear cells of donor origin and more than 90% lymphocytes of donor origin ( Supplemental Figure 1A ). Immune reconstitution was regularly monitored (lymphocyte subset analysis results are shown on  Supplemental Figure 1B ), and the patient achieved stable CD4+ and CD8+ T-cell counts above 200 cells/mL after 2 months ( Supplemental Figure 1C ).
Initial presentation and diagnostic hallmarks. (A) Hypercellular bone marrow with suppressed erythroblastic lineage. (B) Erythematous-exfoliative skin lesions.
fimmu-13-1033338-g002.jpg
PMC9626757_02_fimmu-13-1033338-g002.jpg
f2
The patient showed generalized erythematous-small lobular skin eruptions, with exfoliation located mainly on the face ( Figure 2B ), conjunctivitis of Staphylococcus aureus origin, and enlarged cervical and inguinal lymph nodes of up to 1 cm diameter.
PMC9626757_02
Initial presentation and diagnostic hallmarks. (A) Hypercellular bone marrow with suppressed erythroblastic lineage. (B) Erythematous-exfoliative skin lesions.
fimmu-13-1033338-g002.jpg
PMC9626757_02_fimmu-13-1033338-g002.jpg
f2
The patient showed generalized erythematous-small lobular skin eruptions, with exfoliation located mainly on the face ( Figure 2B ), conjunctivitis of Staphylococcus aureus origin, and enlarged cervical and inguinal lymph nodes of up to 1 cm diameter.
PMC9626757_03
Diagnostic key-tests in the LIG1 deficiency patient. (A) Distribution of Vbeta chain of the TCR receptor is oligoclonal with a significantly increased percentage of Vbeta2 and Vbeta12 chains among CD4 lymphocytes. (B) Clonogenic survival assay results. Fibroblasts cultured from skin biopsies of the patient and an Artemis-deficient SCID patient were exposed to increasing dose of irradiation and the percentage survival (axe Y) was determined after 8 days. S1- sample 1, S2- sample 2. RAG1 SCID patient sample was used as a control. (C) The cDNA sequencing results showing the splice site variant in the LIG1 which leads to an insertion of sixteen nucleotides in the exon 9 resulting in a shift of a reading frame and a premature protein termination at position 260.
fimmu-13-1033338-g003.jpg
PMC9626757_04_fimmu-13-1033338-g003.jpg
f3
In order to verify whether the c.776 +5G>T variant affected mRNA splicing, direct cDNA sequencing was executed. It was found that the splice-variant resulted in an insertion of 16 nucleotides in intron 9, leading to a premature protein synthesis termination at position 260 ( Figure 3C ).
PMC9626757_04
Diagnostic key-tests in the LIG1 deficiency patient. (A) Distribution of Vbeta chain of the TCR receptor is oligoclonal with a significantly increased percentage of Vbeta2 and Vbeta12 chains among CD4 lymphocytes. (B) Clonogenic survival assay results. Fibroblasts cultured from skin biopsies of the patient and an Artemis-deficient SCID patient were exposed to increasing dose of irradiation and the percentage survival (axe Y) was determined after 8 days. S1- sample 1, S2- sample 2. RAG1 SCID patient sample was used as a control. (C) The cDNA sequencing results showing the splice site variant in the LIG1 which leads to an insertion of sixteen nucleotides in the exon 9 resulting in a shift of a reading frame and a premature protein termination at position 260.
fimmu-13-1033338-g003.jpg
PMC9626757_04_fimmu-13-1033338-g003.jpg
f3
In order to verify whether the c.776 +5G>T variant affected mRNA splicing, direct cDNA sequencing was executed. It was found that the splice-variant resulted in an insertion of 16 nucleotides in intron 9, leading to a premature protein synthesis termination at position 260 ( Figure 3C ).
PMC9626757_05
PMC9626757_06
The timeline of case report.
fimmu-13-1033338-g001.jpg
PMC9626757_06_fimmu-13-1033338-g001.jpg
f1
The patient developed mixed hematopoietic chimerism that stabilized at the level of 60-70% mononuclear cells of donor origin and more than 90% lymphocytes of donor origin ( Supplemental Figure 1A ). Immune reconstitution was regularly monitored (lymphocyte subset analysis results are shown on  Supplemental Figure 1B ), and the patient achieved stable CD4+ and CD8+ T-cell counts above 200 cells/mL after 2 months ( Supplemental Figure 1C ).
PMC9626757_07