Clinical Study And Exclusive Genetic Mapping On X Chromosome In The X-linked Dominant Inherited Alport's Sydrome

Objective To study the hereditary mode and clinical characteristics and to detect mutations of gene COL4A5 encoding type IV collagen a5 chain among family members of the X-linked dominant inherited Alport's syndrome ( AS ) pedigree of China.Methods All of family member (38) were scanned by physical examination and laboratory. Two propositus got biopsy and pathological examination (optical microscope and electronic microsope). Genomic DNA from 35 members of the pedigree of Alport's syndrome were collected. All of 51 exons of COL4A5 gene were amplified by polymerase chain reaction (PCR) with the primers synthesized according to the published flanking intervening sequences. The PCR products were further analyzed by agarose gel electrophoresis and single strand conformation polymorphism (SSCP) analysis. The PCR products showing polymorphism by SSCP analysis were directly sequenced. Suspectable exons were analysed with inversion sequence.Results 6 males and 9 females of the family were diagnosed AS by clinical manifestations, family history and/or renal biopsy (2 propositus). 4 patients were died of end stage renal disease (ESRD). 1 patient received kidney transplantation. The other family members manifested with normal renal function. 22/38 cases had hematuria, 11 of which manifested with proteinuria also. The hearing loss was detected in 6/38 and ocular lesion in 20/38 of family members. By PCR-SSCP analysis, 17 PCR products were identified with different mobility of single strand DNA in propositus. 9 suspectable mutations were revealed with DNA sequencing analysis. They were not be approved by inversion sequencing analysis.Conclusion The incidence of hematuria and ophthalmopathy is higher. Patient have possible only hematuria. Bidirectional sequencing analysis must be taken to search mutations of target gene. No mutions was found on exons of gene COL4A5.