The Study Of Clinicopathology And COL4A5Gene Mutations In Children With Alport Syndrome

Objective:To analyze the clinical and pathological characteristics of children with Alport Syndrome （AS） and collect2families of X-linked Alport Syndrome （XLAS）,also detect the mutation in51exons of COL4A5gene.Methods:1.We collected the clinical data of13children with AS, also collected the results about optical microscopy examination、 immunofluorescence examination and electron microscopy examination in kidney tissues of12children with AS.2. We investigated2XLAS families and mapped the family pattern, Meanwhile, we collected the clinical features and specimen of the members in2families.3. We carried out indirect immunofluorescence staining of the IV collagen a chain of EBM in all the members in2families.4. Peripheral blood leukocyte DNA was etracted from all the members in2families. We used PCR-DNA direct sequencing methods to detect mutations of51exons in COL4A5Gene.Results:1. The average age of13children with AS was4.46±2.89years old, and no statistical difference between males and females; all the children had hematuria,10of them combined with proteinuria. One AS boy had congenital cataract,4AS children had hearing loss,7AS children had other rare clinical symptoms. There were no specificity consequences in other conventional laboratory results, and the renal ultrasound abnormalities associated with proteinuria.2.The results was variegated in optical microscopy examination, glomerular swelling、inflammatory cells infiltration、hyperplasia of mesangial cells and glomerular epithelial cells degeneration showed in most patients,7AS children had glomerular segmental sclerosis、global stiffness and renal interstitial fibrosis;2AS children had negative staing in each immunofluorescence examination, IgM、Fib positive staing existed in several AS children; all of AS children had thickened GBM in electron microscopy examination,8AS children had delaminated and split GBM,8AS children had podocyte fusion,5AS children showed electronic sediments in GBM;2AS children with indirect immunofluorescence staining of the â…£ collagen a5chain of GBM showed negative staing.3. There were no specificity consequences in clinical features and conventional laboratory results in2XLAS families.4.The results of indirect immunofluorescence staining of the â…£ collagen α chain of EBM:IF revealed a continuous linear staining along EBM with anti-α1（Ⅳ） antibody in all the members of2families; IF revealed a negative staining along EBM with anti-α5（Ⅳ） antibody in â…¢:5, the proband of the family A, while â…¡:3、Ⅲ:4revealed the segmental staining, â…¡:4、Ⅲ:3revealed continuous linear staining; IF revealed a continuous linear staining along EBM with anti-α5（Ⅳ） antibody in all the members of the family B and nomal controls.5. The results of direct sequencing of51exons in COL4A5Gene:a deletion of27nucleotides （COL4A5C.39904016del CCC...TCC） was found at exon41in â…¢:5、Ⅱ:3、Ⅲ:4, while no variant was found in the51exons at â…¡:4、Ⅲ:3of family A; no variant was found in the51exons of COL4A5gene of each members of family B.Conclusion:1. The clinical manifestation was variegated in children with Alport Syndrome, and hematuria associated with proteinuria appeared in most patients. Hearing loss and ocular changes associated with proteinuria and renal tissue fibrosis.2. In exon41, a deletion of27nucleotides（COL4A5C.3990₄016delCCC...TCC） was found. This deletion induced the clinical features of the family and was reported for the first time.