Alternative titles; symbols
ORPHA: 654;
Cytogenetic location: 17q12-q21 Genomic coordinates (GRCh38): 17:33,500,001-52,100,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q12-q21 | Wilms tumor, type 4 | 601363 | Autosomal dominant | 2 |
For a general phenotypic description and discussion of genetic heterogeneity of Wilms tumor, see WT1 (194070).
Rahman et al. (1996) described a large Canadian family with 7 confirmed cases of Wilms tumor in 3 generations. No congenital abnormalities or other cancers had been observed in the family. The average age of presentation was 5 years (age range of 2 to 12 years), which is older than the average age of diagnosis of sporadic WT (3 to 4 years). Typical triphasic histology with stromal, blastemal, and epithelial elements was found in 5 tumors, while the sixth tumor was predominantly myogenic. Five tumors were reported to be unilateral. The myogenic WT was reported to be bilateral at preoperative CT scan. However, at surgery one kidney appeared normal and no biopsy was performed. The predominance of unilateral WTs in this pedigree was consistent with reports from other WT families.
Rahman et al. (1998) analyzed the phenotype of 16 WT patients from families linked to the 17q locus. The patients presented at a significantly older age and at a significantly later stage than both patients with sporadic WT and 6 cases from 2 families unlinked to either 17q or 11p13 (WT1).
Rahman et al. (1996) carried out a genomewide linkage search in a Canadian family with 7 confirmed cases of Wilms tumor and provided strong evidence for the localization of a familial WT predisposition gene, which they symbolized FWT1, to an 18-cM interval on 17q12-q21. They stated that this was the first familial WT locus identified.
Rahman et al. (1998) provided confirmation that the FWT1 locus contains a Wilms tumor susceptibility gene. They analyzed further cases in the original family and detected strong evidence of linkage to the 17q12-q21 region in an unrelated pedigree with 7 cases of Wilms tumor. Analysis of 11 smaller WT families confirmed that there is genetic heterogeneity in familial WT, as 3 families exhibited strong evidence against linkage to FWT1. One of these were subsequently found to have a predisposing WT1 mutation. However, the other 2 families showed evidence against linkage to both FWT1 and WT1, suggesting that at least one further familial WT gene exists.
Rahman, N., Abidi, F., Ford, D., Arbour, L., Rapley, E., Tonin, P., Barton, D., Batcup, G., Berry, J., Cotter, F., Davison, V., Gerrard, M., and 17 others. Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1. Hum. Genet. 103: 547-556, 1998. [PubMed: 9860296] [Full Text: https://doi.org/10.1007/pl00008708]
Rahman, N., Arbour, L., Tonin, P., Renshaw, J., Pelletier, J., Baruchel, S., Pritchard-Jones, K., Stratton, M. R., Narod, S. A. Evidence for a familial Wilms' tumour gene (FWT1) on chromosome 17q12-q21. Nature Genet. 13: 461-463, 1996. [PubMed: 8696342] [Full Text: https://doi.org/10.1038/ng0896-461]