Rhabdoid tumour of the kidney: imaging findings.

BACKGROUND: Rhabdoid tumour of the kidney (RTK) is a rare tumour, but it is the most aggressive malignant neoplasm of the kidney in children. OBJECTIVE: To analyse the radiological findings of RTK in children. MATERIALS AND METHODS: The clinical and radiological findings in seven children (age range 6 months to 4.7 years; median 18 months) with pathologically proven RTK were retrospectively reviewed. We analysed tumour size, tumour location, tumour margin, subcapsular haematoma, tumour necrosis, haemorrhage, calcification and lymphadenopathy. RESULTS: Tumour size varied from 5 to 12 cm. Four tumours were located mainly in the central portion of the kidney, while three tumours were mainly sited peripherally. The margins of the tumour were ill-defined in four (57%) of seven cases, a lobulated tumour surface was depicted in all seven (100%), subcapsular haematoma was present in four (57%), tumour necrosis or haemorrhage in seven (100%), calcifications in three (43%) and retroperitoneal lymphadenopathy in four (57%). CONCLUSIONS: Imaging findings of RTK are subcapsular haematoma, a lobulated surface of the tumour, calcification and tumour necrosis or haemorrhage.

A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, "Osaka," in Asians.

Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by hypergalactosemia and cataract formation. Through mass screening of newborn infants, we identified a novel and prevalent GALK variant (designated here as the "Osaka" variant) associated with an A198V mutation in three infants with mild GALK deficiency. GALK activity and the amount of immunoreactive protein in the mutant were both 20% of normal construct in expression analysis. The K(m) values for galactose and ATP-Mg(2+) in erythrocytes with homozygous A198V were similar to those of the healthy adult control subjects. A population study for A198V revealed prevalences of 4.1% in Japanese and 2.8% in Koreans, lower incidence in Taiwanese and Chinese, no incidence in blacks and whites from the United States, and a significantly high frequency (7.8%; P < .023) in Japanese individuals with bilateral cataract. This variant probably originated in Japanese and Korean ancestors and is one of the genetic factors that causes cataract in elderly individuals.

US identification of the anal sphincter complex and levator ani muscle in neonates: infracoccygeal approach.

PURPOSE: To identify the anal sphincter complex and levator ani muscle at transperineal ultrasonography (US) with the infracoccygeal approach. MATERIALS AND METHODS: Infracoccygeal US was performed with a 7-MHz linear-array transducer in 40 healthy neonates. The babies were placed in the supine position, and both legs were drawn up to the chest. The buttocks were accordingly lifted up. The approach site was just inferior to the coccyx and posterior to the anus. Scanning was performed to obtain transverse images of the anorectal area. The thickness of the anal sphincter complex and the puborectalis muscle were measured. RESULTS: Infracoccygeal US revealed the internal anal sphincter (IAS), the external anal sphincter (EAS), and the puborectalis muscle in all babies. The IAS and EAS were depicted as inner and outer hypoechoic ringlike structures, respectively. A round, hyperechoic space (intersphincteral space) was present between the hypoechoic IAS and EAS. The puborectalis muscle was identified as a U-shaped hypoechoic structure. The bulbocavernosus and ischiocavernous muscles were also identified. Mean thicknesses were as follows: IAS, 1.3 mm +/- 0.3 (SD) (range, 0.8-1.9 mm); EAS, 1.6 mm +/- 0.3 (range, 1.2-2.3 mm); and puborectalis muscle, 1.1 mm +/- 0.3 (range, 0.6-1.9 mm). CONCLUSION: Infracoccygeal transperineal US is an excellent diagnostic modality for demonstrating the anal sphincter complex and levator ani muscle in neonates.

Novel mutations, including the second most common in Japan, in the beta-hexosaminidase alpha subunit gene, and a simple screening of Japanese patients with Tay-Sachs disease.

Two novel mutations of the beta-hexosaminidase alpha subunit gene were identified in Japanese patients with the infantile form of Tay-Sachs disease. One mutation was a one-base deletion at nt613C, which generated a stop codon at two codons downstream, in three unrelated patients. The other mutation was a one-base substitution of G-to-A at IVS 5, +1, which caused a splicing abnormality, in one patient. A missense mutation of R170W, which has already been reported in other ethnic groups, was also newly identified in one patient. In 1993, the most common mutation (IVS 5, -1G-->T) in Japanese patients with Tay-Sachs disease was reported as the major mutation in Japan accounting for 80% of 56 mutant alleles from 28 unrelated patients. The deletion of nt613C was the second most common mutation, accounting for 5% of the mutant alleles. The previously reported mutation IVS 5, -1G-->T and the nt613C deletion found in this study together accounted for 85% of the mutations causing Tay-Sachs disease among Japanese. Since these two mutations were located in or close to exon 6 and since they abolish Fok I (IVS 5, -1G-->T) and Sfa NI (nt613C deletion) restriction sites, respectively, they were screened rapidly by single polymerase chain reaction followed by digestion with these enzymes.

Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3'-splice site selection and cause Sandhoff disease.

Four unrelated Japanese patients with infantile Sandhoff disease (beta-hexosaminidase beta-subunit deficiency) have been studied for the molecular basis of their severe phenotype. Two patients had complex base substitutions; one patient was homoallelic for a triple mutation (P417L, K121R, and S255R) and the other was a compound heterozygote of a double (P417L and K121R) mutation and the triple mutation. K121R is known to be a functional polymorphism, while P417L (exon 11, +8 C-->T) generates predominantly an abnormally spliced mRNA at base +112 of exon 11 and has been described in two patients with a juvenile form of the disease. The mild phenotype is attributed to the presence of a small amount of normally spliced mRNA. S255R is a novel mutation without prior description in the literature. An expression study of the normally spliced cDNA with the double and the triple mutations gave about 70% and 30% of normal activity, respectively. This finding suggests that S255R further reduces the catalytic activity of the already below-threshold amount of normally spliced mRNA and accounts for the more severe phenotype in our patients. In the other two patients, a novel disease-causing base transition was found within intron 10, away from the intron/exon junction (-17 a-->g). This mutation caused abnormal 3' splicing at position -37 of intron 10, and no normally spliced product was detectable upon RT-PCR analysis. We noted an unusually low splice site score (61.8) for the exon 10/intron 11 junction and suspected that this might be partially responsible for the aberrant splicing in these mutations. To test this hypothesis, we constructed four chimeric cDNAs all with an additional intron 10 inserted and evaluated their splicing efficiency. They, respectively, had the normal sequence, P417L (exon 11, +8 C-->T), the intronic mutation (-17 a-->g), and the intronic mutation with an artificially engineered intron 10/exon 11 junction of a higher splice site score (85.1). Of the total transcripts, 67% and 32% were correctly spliced in the normal chimeric construct and P417L, respectively, while no normally spliced product was generated either in the chimeric construct with -17 a-->g or in that with a high splice site score. The sequence around the adenosine -17 residue upstream of the normal acceptor splice site in this report, UGCAAU (-21 to -16), matches the consensus branchpoint sequence YNYRAY (Y, pyrimidine; R, purine; N, any base) reported in the literature. The mutation in this study is most likely to abolish lariat formation because the artificial site of the high splice site score did not improve splicing efficiency.