Identification of a novel COL4A4 mutation in a family with thin-basement-membrane nephropathy and the pathogenic mechanism
10.3760/cma.j.issn.1001-7097.2016.02.003
- VernacularTitle:薄基底膜肾病家系新发COL4A4基因突变及致病机制探究
- Author:
Guoqing ZHANG
;
Nan LIN
;
Min GUO
;
Yan XU
- Publication Type:Journal Article
- Keywords:
Hematuria;
Collagen type Ⅳ;
Mutation;
Thin-basement-membrane nephropathy
- From:
Chinese Journal of Nephrology
2016;32(2):94-98
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore a new pathogenic gene mutationin in COL4A3 and COL4A4 genes of a family with thin-basement-membrane nephropathy (TBMN), and explain its mechanism.Methods Genomic DNA was extracted from blood samples.Mutation screening for all the exons in COL4A3 and COL4A4 of the proband was carried out by direct PCR sequencing.The sequences of the proband were compared with standard sequences in GenBank.After identifying the mutation in COL4A4, screening for the mutation site in 200 healthy controls and the rest of family members were conducted.RNA sequence of the proband was analyzed by reverse transcription PCR and TA cloning.The positive clones were sequenced for RNA screening.Results There was a G to A mutation in the 1459 site of COL4A4 (c.1459+G ＞ A) in the proband, her mother, and the elder sister, whereas the mutation was not found in other family members and healthy people.RNA screening showed that the COL4A4 (c.1459+G ＞ A) mutation was a heterozygous substitution in position + 1 of exon 21, in the splicing region.This mutation leaded to eliminating of exon 21 from the COL4A4 mRNA, causing the exon 21 deletion and frameshift mutation following the exon 20 in its amino acids sequence.Conclusions It is described that COL4A4 (c.1459+G ＞ A) is a new pathogenic mutation in TBMN, which further help understanding the pathogenesis and clinical diagnosis of TBMN.
