A Rare Coincidence of Sitosterolemia and Familial Mediterranean Fever Identified by Whole Exome Sequencing.

Whole exome sequencing (WES) technologies have accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. We encountered a 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial LDL cholesterol=609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. Both her phenotypes seemed to co-segregate in a recessive manner. We performed WES on this patient, who was considered a proband. Among 206,430 variants found in this individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 Genome (Asian population). Filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool, we successfully narrowed down the candidates to the compound heterozygous mutations in the ABCG5 gene (c.1256G＞A or p.Arg419His/c.1763-1G＞A [splice acceptor site]) and to the double-compound heterozygous mutations in the MEFV gene (c.329T＞C/C or p.Leu110Pro/c.442G＞C/C or p.Glu148Val). The patient was genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time. Such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases.

Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation.

Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).

Indications for ureteropyeloscopy based on radiographic findings and urine cytology in detection of upper urinary tract carcinoma.

OBJECTIVE: To verify the indication of diagnostic ureteropyeloscopy based on clinical features for upper urinary tract urothelial cancer with over 100 patients and over a 10-year series. METHODS: From January 1997 to December 2008, consecutive 129 units in 124 patients underwent ureteropyeloscopy to obtain a definitive diagnosis of upper urinary tract cancer or to rule out a malignancy. Patients were divided into four subgroups based on voided urine cytology and preoperative radiographic findings: group A (n = 8), positive urine cytology and positive radiographic findings; group B (n = 4), positive cytology and negative radiographic findings; group C (n = 55), negative cytology and positive radiographic findings and group D (n = 62), gross hematuria originating from the upper urinary tract with negative cytology and negative radiographic findings. Ureteropyeloscopic findings were compared with radiographic and cytological results. Adverse effects were also investigated. RESULTS: In group A, all patients had confirmed cancer. In group B, one revealed small cancer and the remaining three confirmed carcinoma in situ by biopsy with ureteropyeloscopy. In groups C and D, 33 patients (60%) and four (6.5%) revealed cancer. Seventy-eight patients out of 80 (97.5%) in groups C and D were confirmed to have benign disease. No patient was found with malignancy during follow up after negative finding of ureteropyeloscopy. CONCLUSIONS: Ureteropyeloscopy can help in detecting upper urinary tract cancer or to rule out malignancy for patients with negative voiding cytology. However, ureteropyeloscopy is redundant for patients with positive radiographic findings and positive voiding cytology.

Molecular genetic and bile acid profiles in two Japanese patients with 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficiency.

We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum [gamma]-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3[beta]-hydroxy-[DELTA]5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3[beta]-hydroxy-[DELTA]5-bile acids such as 3[beta],7[alpha]-dihydroxy- and 3[beta],7[alpha],12[alpha]-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3[beta]-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage.

The female partner's satisfaction with sildenafil citrate treatment of erectile dysfunction.

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.

Retroperitoneoscopic nephropexy for symptomatic nephroptosis.

PURPOSE: Recently, laparoscopic nephropexy has been performed using a transperitoneal approach. We evaluated the efficacy of a retroperitoneoscopic technique for symptomatic nephroptosis. PATIENTS AND METHODS: Three men and two women with right nephroptosis underwent retroperitoneal laparoscopic nephropexy. Their symptoms were right flank pain, gross hematuria, or both. The mean body mass index was 18.7. Surgery consisted of complete dissection of the kidney, after which three sutures were placed between the renal capsule at the posterior lateral edge and the psoas or quadratus lumborum muscle. Silk sutures were used in all five patients. RESULTS: Retroperitoneoscopic nephropexy was successful with no intraoperative complications. The mean operative time was 167 minutes, and the mean estimated blood loss was <10 mL in all five patients. The mean convalescence period was 19.6 days. A postoperative urogram with the patients both supine and erect revealed an improvement in renal function, decreased displacement of the kidney (less than one vertebral body), or both. All patients were satisfied with the clinical outcome during an average of 18 months of follow-up. CONCLUSIONS: Retroperitoneoscopic nephropexy is feasible for patients with symptomatic nephroptosis. We recommend nonabsorbable materials such as silk for fixation of the kidney to the psoas or quadratus lumborum muscle.

[The analysis of thymidine phosphorylase examined by ELISA in bladder cancer].

PURPOSE: Some reports suggest that the high level expression of thymidine phosphorylase (TP), which is known as one of angiogenic factors, is related to high malignancy and also poor prognosis in the field of gastrointestinal cancer. So the authors investigated the expression of TP in bladder cancer. MATERIALS AND METHODS: The expression of TP in cancer tissues and normal tissues, which were obtained during transurethral resection of the tumor of 66 patients with initial primary bladder cancer, was examined by enzyme-linked immunosorbent assay (ELISA). And relationship of the TP expression and clinicopathologic factors was investigated. RESULTS: The level of TP expression was significantly high in cancer tissues compared with normal tissues (P < 0.0001). About the level of TP expression of cancer tissues, there was a significant difference between G1 and G3 in grade (P = 0.0099), Ta and T2 or greater (P = 0.0059), Ta, T1 and T2 or greater (P = 0.0157) in T stage, papillary and non-papillary in surface form (P = 0.0056), pedunculated and sessile in tumor shape (P = 0.0458), and 1 cm or under and 3 cm or greater in size (P = 0.0267). The level was higher in latter, respectively. About the level of TP expression of normal tissues, the level was significantly higher in the cases with sessile tumor than the cases with pedunculated tumor (P = 0.0078). CONCLUSION: There is correlation between the level of TP expression of cancer tissues and their grade of malignancy, so we can expect that the level of TP expression of cancer tissues will be a prognostic factor. And what does it mean in the fact that the level of TP expression of normal tissues in patients with sessile tumor is higher? It should be clear after accumulation of the cases and collecting the episodes in the follow-up period.