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  • A novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney.

A novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney.

American journal of nephrology (2008-06-27)
Leping Shao, Liqiu Liu, Zhimin Miao, Hong Ren, Weiming Wang, Yanhua Lang, Shaoheng Yue, Nan Chen
ABSTRACT

Gitelman's syndrome is a mild autosomal recessive disorder caused by inactivating mutations of SLC12A3. However, severe phenotype may be associated with compound heterozygous nonfunctional variants such as frameshift and splicing mutations. Because most multi-exon genes are alternatively spliced as shown by recent studies, SLC12A3, with 26 exons, is likely to be alternatively spliced as well. A case of Gitelman's syndrome with both physical and mental retardation was investigated by genetic analysis. In addition, the alternative splice variants of SLC12A3 were screened by RT-PCR. A novel intron 7 and exon 8 boundary mutation (a successive 13-nucleotide transition: intron 7 as -1 G>A plus exon 8 +1 to +12 delCGGACATTTTTGinsCCGAAAATTTT) was identified in this patient besides a missense mutation Thr60Met. Further cDNA analysis revealed the novel mutation led to skipping of exons 7 and 8. Furthermore, we found an aberrant splice product skipping of exon 7 and identified two high-abundance alternative splice transcripts. This is the first report of a splice mutation of SLC12A3 with multiple-exon skipping in Gitelman's syndrome. This study provides further evidence for the severe phenotype of Gitelman's syndrome and its association with underlying mutations. Additionally, we demonstrated that the pre-mRNA of SLC12A3 was complex spliced.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
GenElute Blood Genomic DNA Kit, sufficient for 70 purifications
Sigma-Aldrich
GenElute Blood Genomic DNA Kit, sufficient for 350 purifications