Novel frame shift mutations ('A' deletion) observed in exon 9 of Wilms' tumor (WT1) gene in a patient reported with glomerulosclerosis.
Wilms' tumor-suppressor gene-1 (WT1) is a transcription factor that contains four zinc-finger motifs at the C-terminus and plays a crucial role in kidney and gonad development. We have identified primitive glomeruloid formation using immunohistochemistry in a patient who was clinically diagnosed with a Wilms' tumor. In order to understand the involvement of mutations in the WT1 gene, the genomic DNA was isolated from peripheral blood of the patient (18/F). Exon 9 of the WT1 gene was amplified and sequenced. The obtained sequence was BLAST searched against the transcript variants (TV) of the WT1 gene. An amplified exon 9 sequence of the WT1 gene showing similarity with exon 9 of TV-A, F and exon 10 of TV-B, D and E with a deletion of single nucleotide 'A' causing frame shift in the 4th zinc finger domain of the WT1 protein resulted in Wilms' tumor condition. The deletion position is variable with different transcript variants and they are present at: for TV-A c.1592delA, p.468, for TV-F c.1053delA, p.259, for TV-B c.1643delA, p.485, for TV-D c.1652 delA, p.488, and for TV-E c.1095delA, p.273; all these variations resulted in frame shift mutation. In order to substantiate these results in silico analysis was carried out; the structural superimposition of wild type and mutant WT1 structures showed that the mutated region exhibited a different confirmation with RMSD of 1.759Å. Therefore, these results conclusively explain the mutation in the WT1 gene that leads to structural changes contributing to glomerulosclerosis.
Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Santhosh Kumar
SK
Pasupuleti
Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Venkatesh
V
Katari
Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Srikanth
S
Lokanathan
Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Venkateswara Prasad
VP
Uppu
Department of Urology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Syama Sundar
SS
Thummaginjala
Department of Urology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Ram Prasad Reddy
RP
Akkamgari
Department of Urology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Tyagi
T
Ayapati
Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India.
Radhika
R
Kottu
Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP 517507, India. Electronic address: sarmasvims@gmail.com.
Venkata Gurunadha Krishna Sarma
VG
Potukuchi
D000595:Amino Acid Sequence; D005091:Exons; D016368:Frameshift Mutation; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D016415:Sequence Alignment; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics*; D009396:Wilms Tumor / Q000150:complications / Q000235:genetics*
D025721:WT1 Proteins; C583751:WT1 protein, human
Frame shift mutation; Immunohistochemistry; RMSD; Wilms' tumor