title: Skin biopsy is a practical approach for the clinical diagnosis and molecular genetic analysis of X-linked Alport's syndrome.
abstract: A total of 209 unrelated patients of predominantly Han Chinese ethnicity and with X-linked Alport's syndrome, a clinically heterogeneous hereditary nephritis, were enrolled in the present study to evaluate the ability to make a clinical diagnosis and perform molecular genetics analysis using skin biopsy. A negative or mosaic α5(IV) chain staining in the epidermal basement membrane was detected in 86.2% of male and 93.5% of female patients. COL4A5 mutations were identified in 85% of male patients with a negative α5(IV) chain staining pattern in the epidermal basement membrane. With use of skin biopsy and immunostaining, 16.4% of our patients were diagnosed before 3 years of age, and the youngest was diagnosed at 1 year of age. COL4A5 mutations were detected in 22 patients with normal epidermal basement membrane staining for the α5(IV) chain. Analysis of COL4A5 cDNA fragments from skin fibroblasts yielded a mutation detection rate of 83%, which was particularly valuable for identification of cryptic splicing mutations. Furthermore, 83% of COL4A5 mutations identified in the present study were novel. Thus, skin biopsy is a practical approach for the clinical diagnosis and molecular genetic analysis of X-linked Alport's syndrome.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Huijie
authors.initials: H
authors.lastname: Xiao
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhong
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics*; D001706:Biopsy; D015331:Cohort Studies; D024141:Collagen Type IV / Q000032:analysis / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV