PMC3010696_01
Photograph of the patient showing subtle dysmorphic features with high forehead, flat facies, large protruding ears, and large mouth, at the age of 7 years (a) and at the age of 9 years (b). Fungal infection (Candida albicans) of the nails (thumb and middle finger) and dorsum of the hand (c) and around the mouth corners (d).
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fig1
The patient is a 12-year-old Saudi boy (Figure 1) who was brought initially to medical care at the age of 6 months because of delayed developmental milestones. At 18 months of age, the patient was noted to have oral lesions and nail dystrophy (Figures 1(c) and 1(d)).
Superficial esophageal mucosa ((a),(b)) invaded by candidal psudohyphae. Grocott-Methenamine silver (original magnification 200x (a)/400x (b)). Renal biopsy ((c), (d), (e)) shows ischemic glomerular tuft with thick and wrinkled basement membrane (PAS stain 40x) (c) and extensive tubular loss with replacement by fibrosis (Masson trichrome stain 40x) (d). The interstitium shows lymphocytes and plasma cells (arrows) (H&E 40x) (e). The immunofluorescence staining for C3 and C1q is shown in (f) and (g), respectively.
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Because of recurrent vomiting, an upper GI Endoscopy was performed and revealed candida esophagitis (Figures 2(a) and 2(b)). The renal biopsy (Figures 2(c), 2(d), and 2(e)) showed chronic tubular interstitial nephritis with advanced fibrosis. The immunofluorescence demonstrated mesangial deposition of C3 (3+), C1q (2+) (Figures 2(f) and 2(g)), and IgM (1+) (figure not shown) in the glomerulus examined.
Trypsin-Giemsa karyotype 46,XY,del(4)(q33) from peripheral blood cells in the patient, the arrow indicates the abnormal chromosome 4 (a). Metaphase FISH image (b) from peripheral blood hybridized with Vysis 4p/4q subtelomere probes. The small arrow shows the deletion of the 4qsubtel region (red) on the abnormal 4q33 deletion chromosome. The 4psubtel region shows the normal green signals for both chromosomes 4. ish del(4)(q33)(4psubtel+; 4qsubtel-). The array CGH (c) depicting the terminal deletion on long arm of chromosome 4 and its breakpoints. The deletion starts at 177,732,852 and ends at 191,279,059 bp on Chr4 and is nearly 13.5 Mb. There are 72 genes in the region based on NCBI Build 35.1 for Homosapiens.
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fig3
The chromosomal study revealed 46,XY,del(4)(q33) (Figure 3(a)). Fluorescence in situ hybridization (FISH) analysis using the 4P/4Q subtelomere DNA probe confirmed the presence of deletion 4q33 (Figure 3(b)). The array CGH (Figure 3(c)) showed a large deletion that starts at 177,732,852 and ends at 191,279,059 bp on chromosome 4 and refined the terminal deletion to be starting at 4q34.3.