Jie Ding, Fang Wang, Shunhua
Guo, et al.
Department of Pediatrics,
First Hospital, Peking University, Beijing, China
Alport syndrome
(AS) is a hereditary renal disease and caused by mutations of COL4A5 gene which
encodes the type IV collagen a5 chain. This study aimed to analyze the
clinical features of Chinese AS patients and to identify deletions and
mutations of COL4A5 gene in Chinese AS patients which we know little. Fifty
unrelated Alport syndrome (AS) patients (32 males and 18 females) were
analyzed. At the same time, screening for mutations in all the exons (1 to 51)
of the COL4A5 gene was carried out by PCR-SSCP or PCR-direct sequence analysis
on genomic DNA from 33 unrelated patients with X-linked AS (22 males and 11
females). The analysis of clinical data showed 96% of patients presented with
hematuria while the urinary RBC morphology examination revealed 84% of
glomerular hematuria. Eighty-two percent of patients had proteinuria, of whom
22% with a nephrotic level proteinuria. The hearing impairment occurred in 34%
of patients undertaken the pour-tone audiometry. The hearing loss did not
parallel with the renal insufficiency. The occular lesions were found in 18% of
patients examined and may not accompany with the hearing loss. About 82% of
patients belonged to the juvenile kindred. There was 32% of patients without a
positive family history. The majority result (94%) of detecting a5 (IV) chain
on the epidermal basement membrane (EBM) supported the AS diagnosis. PCR-SSCP
analysis showed a mobility shift in 5 of 16 patients and 4 female family
members. DNA sequence analysis revealed 3 missense mutations in exons 17, 20
and 26, 2 silent mutations in exon 39 and 46, and a C®A substitution in intron 3. PCR-Southern
hybridization analysis proved a AS boy with a large deletion of the paired
COL4A5 and COL4A6 genes. Chinese AS patients characterized clinically with
hematuria, heavy proteinuria, a lower rate of both hearing loss and ocular
lesions, and more juvenile types. Mutations in Chinese AS patients mainly were
small mutations while a large deletion involving the 5’ part of both COL4A5 and
COL4A6 genes was identified.