PMC9373126_01
(a) and (b) Area of localized scaly dermatitis and clubbing. (c) Histological
findings in the duodenum. Low power view revealing moderate villous
shortening and intraepithelial lymphocytosis. (Hematoxylin & Eosin
stain, 5x). (d) Dermatitis. Skin biopsy showed superficial and deep moderate
mononuclear infiltrate (Hematoxylin & Eosin stain, 10x).
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Arabian boy of consanguineous parents first presented in 2009 at the age of 7 months with chronic diarrhea, poor weight gain, malnutrition, and an eczematous skin rash. Anti-tissue transglutaminase IgA was slightly elevated [39.3 units, upper limit of normal (ULN) = 0-20] and mucosal biopsy of the duodenum showed mild villous atrophy and nonspecific inflammation [Figure 1(c)]. Skin manifestations were progressive, involving the whole skin surface with areas of localized dermatitis and scaling [Figure 1(a) and (b)]. Skin biopsy revealed mild hyperkeratosis with foci of lymphocytic exocytosis and interstitial chronic inflammatory infiltrate, mainly consisting of lymphocytes, with perivascular and peri-appendiceal aggregation seen mainly in the superficial and deep layers of the dermis [Figure 1(d)].
Granulomatous hepatitis. Some of the portal tracts contain ill-defined
noncaseating granulomas formed of epithelioid histiocytes that are
surrounded by dense mononuclear infiltrate (Hematoxylin & Eosin stain,
20x).
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Percutaneous liver biopsy was performed, which showed expansion of the portal tracts and distension with chronic inflammatory cells, mainly lymphocytes and occasionally eosinophils, along with an ill-defined granuloma surrounded by dense inflammatory cells (Figure 2).
A multigeneration family pedigree showing the autosomal recessive mode of
inheritance of IL2RA defect in the patient.
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Figure 3 shows the family pedigree of the patient being studied.
Bioinformatic analysis of the human IL2RA. Images (a) and
(b) show the RNA secondary structure predictions for wild-type and mutant
mRNAs (c.504 C>A) in the form of a mountain plot (MP) representation of
minimum free energy (MFE), thermodynamic ensemble (pf), and the centroid
structure predictions, respectively. The color gradient in the scale of 0 to
2 represents the MFE calculations of nucleotide base pairing. The MP
representation shows the secondary structures in a height
versus position in which the helices are represented in
slopes, loops in plateaus, and hairpin loops in the peaks. The bottom graph
represents the entropy of predicted RNA structure in which higher entropy
means the RNA structure has lower stability. Image (c) shows that the c.504
C>A variant falls in the complement control protein (CCP domain). Also,
the location of Cys168Ter is shown in the 3D model.
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Findings from mRNA secondary structure of IL2RA predictions have indicated no significant changes in the thermodynamic stability of the mRNA folding pattern due to c.504 C>A variant (Figure 4).