Artículos de revistas
Wt1 Haploinsufficiency Supports Milder Renal Manifestation In Two Patients With Denys-drash Syndrome
Registro en:
Sexual Development. Karger, v. 11, p. 34 - 39, 2017.
1661-5425
1661-5433
WOS:000395907200004
10.1159/000454821
Autor
Guaragna
Mara S.; Ribeiro de Andrade
Juliana G.; Carli
Brbara de Freitas; Belangero
Vera M. S.; Maciel-Guerra
Andrea T.; Guerra-Junior
Gil; de Mello
Maricilda P.
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Denys-Drash syndrome (DDS) is characterized by nephropathy, genital abnormalities, and predisposition to Wilms' tumor. DDS patients usually present heterozygous de novo germline WT1 mutations. The WT1 gene comprises 10 exons encoding the N-terminal transactivation and the C-terminal DNA-binding regions. Two unrelated patients with genital ambiguity and Wilms' tumor were analyzed by sequencing of the WT1 gene, and 3 mutations in exon 1 were identified of which 2 are novel. Patient 1 carried a c.555delC mutation that causes a frameshift and a premature stop codon. Patient 2 carried both c.421A>C and c. 424C>T aberrations that lead to the missense p.Lys141Gln and the nonsense p. Lys142 * mutation, respectively. As both patients were heterozygous for the mutations, we tested their parents who did not carry any mutation. Therefore, the 3 WT1 mutations occurred de novo in both patients. Heterozygous mutations result in WT1 haploinsufficiency as they impair protein production. They are associated with a milder DDS phenotype as observed in the patients studied here. 11 1 34 39 Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP-2012/51109-0] Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [CNPq-478444/08-7, 141072/2010] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)