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The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor
Author(s) -
Barbosa Angela S.,
Hadjiathanasiou Charalambos G.,
Theodoridis Charalambos,
Papathanasiou Astéroula,
Tar Attila,
Merksz Miklós,
Györvári Borbála,
Sultan Charles,
Dumas Robert,
Jaubert Francis,
Niaudet Patrick,
MoreiraFilho Carlos A.,
Cotinot Corinne,
Fellous Marc
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1999)13:2<146::aid-humu7>3.0.co;2-i
Subject(s) - exon , wilms' tumor , missense mutation , point mutation , biology , genetics , mutation , stop codon , intron , splice site mutation , gene , rna splicing , cancer research , alternative splicing , rna
Denys‐Drash and Frasier syndromes are rare human disorders that associate nephropathy with gonadal and genital abnormalities. In DDS there is a predisposition to Wilms' tumor. Heterozygous point mutations in the Wilms' tumor, type 1 gene ( WT1 ), particularly those altering the zinc finger (ZF) encoding exons, have been reported in most DDS patients, while mutations in intron 9 of the same gene cause FS. This paper describes two cases of DDS, one FS and one patient with Wilm's tumor and intersex genitalia, in which mutations were searched by sequencing the exons 8 and 9 of WT1 gene. Patient 1 carried a missense point mutation in exon 8 (ZF2), converting a CGA‐Arg codon to a TGA‐stop codon. Patient 2 presented a single nucleotide deletion within exon 9 (ZF3) introducing a premature chain termination at codon 398. Patients 3 and 4 had a C→T transition at position +4 of the second alternative splice donor site of exon 9 (this mutation was detected in peripheral blood and in tumor derived DNA of patient 3). However, patient 3 had previously developed a Wilms' tumor. This is the first case of Wilms' tumor development in a phenotypically and genetically confirmed case of FS. Hum Mutat 13:146–153, 1999. © 1999 Wiley‐Liss, Inc.