PMC9247144_01
Timeline of the patient's clinical history. Items are classified into signs and symptoms (blue), diagnoses (red), laboratory tests and imaging (purple), and treatments (green). The patient's images are included with the explicit consent of the patient and his parents.
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f1
He was seen in our Clinical Genetics Department at 3 months of age and was noted to have a narrow forehead, horizontal eyebrows, synophrys, deep-set eyes, epicanthus, wide nasal ridge, anteverted nares with underdeveloped alae nasi, and a thin upper lip vermilion with smooth philtrum (Figure 1). Malignancy and clonal rearrangements were excluded by lymph node biopsy (Figure 1).
Molecular and functional studies. (A) Array CGH-based identification of the 13-Mb deletion in the 4q22.2-q24 chromosomal region. Patient DNA was labeled with cyanine 3 (Cy3, red dots) and control DNA with cyanine 5 (Cy5, blue dots). The image is reported as the ratio of Cy5 and Cy3 fluorescence intensity. The list of genes encompassed by this deletion is shown. Genes that are likely related to the patient's non-immune clinical phenotype are in bold. The NFKB1 gene is highlighted in red. (B) NF-kB pathway evaluation by western blot. NFKB1 p105/p50 expression and activation were evaluated in PBMC-derived protein extracts from the patient and a healthy donor. For a better comparison between the healthy donor and patient, we quantified the p105 and p50 bands using the ImageJ software. The quantification reflects the relative amounts as a ratio of each protein band relative to the lane's loading control (beta-actin): p105 patient (0': 0.24, 30': 0.20, 60': 0.22); p105 healthy donor (0': 0.79, 30': 0.76, 60': 1.10). p50 patient (0': 1.07, 30': 1.12, 60': 0.74); p50 healthy donor (0': 1.39, 30': 1.27, 60': 1.41).
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f2
Because of the patient's complex phenotype involving immunological abnormalities, dysmorphic features and developmental changes, microarray-based comparative genomic hybridization (aCGH) was performed in 2010 (Supplementary Methods), which identified a 13.03-Mb heterozygous deletion on chromosome 4q22.2-q24 (ISCN formula to date: arr [GRCh37] 4q22.2 q24 (94264597_107296595)x1) (Figure 2A).