A group of the scientists from Switzerland, Germany and Israel have described the cases of three infants with similar symptoms. After genetic analysis of a samples harvested from the young patients, a mutation of α3 integrin was found.
Integrins are transmembrane molecules consisting of subparticles α and. They are adhesion molecules and enable interaction between cytoskeleton and extracellular matrix. The integrins are very important during embryogenesis, they route a right direction of the cell migration, and participate at binding of the blood cells. Integrins regulate a shape of the cells and are responsible for immune cell migration (immuneresponse). (2,3)
The first described patient was a boy, second child of the 42-yeard old 2-gravida, 2-para, born at 41 week and 4 days of pregnancy (the delivery induced by oligohydramnion and child postmaturity). No organ diseases were present in the family. Immediately after the labor he has developed tachypnoe and serious respiratory distress. Thorax radiography showed reticulonodular changes. At 13 day of the hospitalization the kidney function had worsen (GFR<10 ml/min/1,73m2 ) and nephritic syndrome appeared. Ultrasonography of the abdomen showed small hyperechoic kidney. The respiratory insufficiency was persistent. A kidney bioptat harvested at 1 month of life showed globally atrophic glomeruli. Since 3 month skin problems had developed. The skin was more brittle, bullous, prone to exfoliation, even due to small injuries. The boy died because of lung infection at the age of 7,5 months.
The second described patient was a girl, only one affected from nine children of the consanguineous parents. At the day 2 after delivery respiratory distress and cyanosis had developed. At 6 week thorax radiography showed diffuse interstitial changes on both sides. Renal insufficiency had also developed. The girl died when she was 2 months old.
The third case war a girl, a daughter of the healthy consanguineous parents. At the age of 2 months a respiratory distress and fever had developed. The thorax scan showed an inflammation of the upper and middle lobe of the right lung. A proteinurie occurred. The kidney bioptat at age of the 5 months indicated segmental glomerulosclerosis. She was dialised until 17th month. Since 4th month occurred annular, erythematic skin leasions, easily prone to bullus-building and to exfoliation. The girl died at the age of 19 months because of multiorgan insufficiency caused by the infection.
Genomonic DNA analysis of leucozytes from peripheral blood showed mutation of ITGA3 (as well in intron as in egzon, dependent on patient). All of the children had homozygotic mutation of ITGA3. Tissue samples from the patients were investigated with light microscopy, transmission electron microscopy and immunohistochemical analysis. The microscopical view of the skin samples was similar to the view of the epidermolysis bullosa skin, but it couldn’t be associated with any described by the human type of epidermolysis bullosa. The skin was only associated with epidermolysis bullosa type in mice devoid of integrin α3. A loss of immunological response to α3 by the first patient’s skin samples was indication of loss of this protein. The loss of α3 protein was also confirmed by flow cytometry of the patient’s keratinocytes.
The pathologies of the lungs, the kidneys, and the skin in mice devoid of α3 are similar to pathologies in the patients however, an inflammation of the lung could be associated more with general immune deficit.
Trias of the congenital symptoms: lung failure, nephrotic syndrome and epidermolysis bullosa indicate on pleiotropic postnatal function of integrin α3. This molecule seems to have an important function because the prognosis of described syndrome are unfortunate.
1) Has Cristina and all, Integrin α3 mutations with kidney, lung and skin disease, N Engl J Med 2012; 366:1508-1514April 19, 2012
2) Kawiak Jerzy and all, Seminaria z cytofizjologii dla studentów medycyny, weterynarii i biologii, Elsevier Urban & Partner, Wrocław 2001, 310-325
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