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, type1 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.
The strategy for morphological investigations in children with acute pyelonephritis (APN) remains debatable. We studied 70 children (median age 2.0 years) admitted with a first episode of pyelonephritis using a high-resolution ultrasound technique (RUS) and compared the results with 99m technetium-dimercaptosuccinic acid (DMSA) renal scintigraphy. The DMSA scan was abnormal in 62 children (89%). However, using a high-frequency transducer we found abnormal sonogram changes in 61 children (87%), consisting of an increased kidney volume in 42, and/or a thickening of the wall of the renal pelvis in 42, and/or a focal hyper- or hypoechogenicity in 36, and/or a diffuse hyperechogenicity in 31 children. Micturating cystourethrography was performed in all children, revealing vesicoureteral reflux (VUR) in 22 (31%). Among those children with VUR, 4 had a normal DMSA scan, 2 an abnormal RUS, and 2 a normal DMSA scan and RUS. Our data suggest that B-mode RUS performed with a high-frequency transducer by a trained radiologist is nearly as sensitive as the DMSA scan in diagnosing renal involvement in children with unobstructed APN and in predicting VUR.
These data suggest that, in the four patients, bilateral congenital anorchia is not related to an anomaly of the opening reading frame sequence of the SRY gene.
The present study reports eight additional mutations in the connexin32 gene associated with the X-linked form of Charcot-Marie-Tooth disease. One of these mutations was found twice in two apparently unrelated families. This form of the disease is demyelinating and dominant. However, patient selection for mutational screening should not be limited to these criteria since presentation can either be familial or sporadic, and some patients may be incorrectly classified as suffering from an 'axonal' form. These new mutations complete our previously published work on 12 other mutations and enable meaningful observation in a representative sample of the French population. Mutations are found in all regions of the gene. The most frequently observed mutations were those affecting arginines and mainly involved CpG sequences. Compared with other sources, some of the mutations were present at a higher frequency in the French population.
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