Detection Of A Novel Mutation In COL4A5 Gene From A Chinese Family With X-linked Alport Syndrome

Basement membrane (BM) is extracellular matrice, type IV collagen molecule is its major structural component, providing a framework for the binding of other basement membrane components. Abnormalities in this basement membrane collagen structure and function are connected to both inherited and acquired diseases.Alport syndrome(AS) is a hereditary kidney disease associated with extrarenal complications, such as sensorineural deafness and eye abnormalities and so on. The disease is caused by mutations in the COL4A3, COL4A4, COL4A5 genes, coding for the type collagen a 3, a 4 and a 5 chains, respectively. Alport syndrome follows an X-linked trait in approximately 80% of the cases, whereas autosomal recessive, autosomal dominant and uniformative pedigrees account for the remainder.By means of PCR and direct sequencing, all 51 exons and their neighbouring intronic sequences of the COL4A5 gene were analyzed to detect mutations in 17 members from a Chinese family with X-linked Alport syndrome(XLAS). At the position 2240 in exon 26, a single-base deletion(2240delC) is found in all male patients, and a heterozygous deletion is found in all female patients, whereas no mutation is found in normal and 80 control individuals. Meanwhlie, the corresponding PCR products of female patients are cloned and sequenced to confirm the results. It is concluded that the 2240delC mutation is the underlying cause of XLAS in this family, not a polymorphism. Furthermore, this single-base deletion mutation in COL4A5 gene is first reported in X-linked Alport syndrome.This work has a significant clinical value by providing the DNA-based analysis of all exons and their neighbouring intronic sequences of the COL4A5 gene in the examined individuals, furthermore, the phenotype-genotype correlations of the patients can be studied.