Germline gene testing of the RET, VHL, SDHD and SDHB genes in patients with pheochromocytoma/paraganglioma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the germline variations of genes RET, VHL, SDHD and SDHB in patients with pheochromocytoma and/or paraganglioma and to evaluate variations of these genes in Chinese patients.@*METHODS@#Patients who were treated in Peking University First Hospital from September 2012 to March 2014 and diagnosed with pheochromocytoma and/or paraganglioma by pathologists were included in this study. Twelve patients were included in total, of whom 11 had pheochromocytoma, and 1 had paraganglioma. Deoxyribonucleic acid (DNA) was extracted from the leukocytes of peripheral blood of the patients. The exons 10, 11, 13-16 of the RET gene, and all exons of VHL, SDHB and SDHD genes and their nearby introns (±20 bp) were amplified with polymerase chain reactions, and the products were sent to a biotechnology company for sequencing. The sequencing results were compared with wildtype sequences of these genes to identify variations. One of the patients was diagnosed with multiple endocrine neoplasia type 2A. A family analysis was performed in his kindred, and his family members received genetic tests for the related variations.@*RESULTS@#Three patients were found to have germline gene variations. A c.136C>T (p.R46X) variation of the SDHB gene was found in a patient with malignant pheochromocytoma. A c.1901G>A (C634Y) variation, as well as c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were found in a patient with multiple endocrine neoplasia type 2A. After a family analysis, five family members of this patient were found to have the same variations. c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were also found in a clinical sporadic patient without evidence of malignancy. A patient with congenital single ventricle malformation and pheochromocytoma was included in this study, and no variation with clinical significance was found in the four genes of this patient.@*CONCLUSION@#25% (3/12) patients with pheochromocytoma or paraganglioma were found to have missense or nonsense germline gene variations in this study, including the c.136C>T (p.R46X) variation of the SDHB gene, the c.1901G>A (C634Y) variation of the RET gene, and c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene. The former two variations have already been confirmed to be pathogenic. The existence of these variations in Chinese patients with pheochromocytoma and/or paraganglioma was validated in this study, which supports the conclusion that genetic testing is necessary to be generally performed in patients with pheochromocytoma and/or paraganglioma.

Diagnostic accuracy of various glomerular filtration rates estimating equations in patients with chronic kidney disease and diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The equations for estimating glomerular filtration rate (GFR) based on creatinine have been found to have limitations and have not been generalizable across all populations. Equations based on cystatin C provide an alternative method to estimate GFR. Whether the equation based on cystatin C alone or combined creatinine would improve GFR estimates has not been validated among Chinese patients with chronic kidney disease (CKD) and diabetes. The aim of this study was to compare the performance of the modification of diet in renal disease (MDRD) equation based on creatinine with the five cystatin C-based formulae for estimation of GFR in patients with CKD and diabetes.</p><p><b>METHODS</b>A total of 166 patients with CKD and 91 patients with type 2 diabetes were enrolled in this study. Cystatin C was measured by using the particle-enhanced immunonephelometric method and estimated formulae proposed by five different investigator teams (Stevens, Ma, Rule, Macisaac and Perkins). The plasma clearance of (99m)Tc-DTPA was determined as measured GFR (mGFR).</p><p><b>RESULTS</b>For CKD patients, the bias and accuracy for the Ma and Macisaac equations were superior compared with the MDRD, and the mean results for the Ma formula were closer to mGFR than the other equations in CKD stages 2 - 5. The differences between Macisaac and mGFR in CKD stages 2 - 4 were significantly less than those in CKD stage 1 or 5. Stevens and Rule's formulae revealed a similar bias and accuracy compared with the MDRD equation. The MDRD formula had a higher accuracy in CKD stages 3 - 5 as compared with the results in other stages. For diabetic patients, the mean results between Macisaac and mGFR were closer than those of other equations in mGFR >or= 90 mlxmin(-1)x1.73 m(-2) stage. In GFR 60 - 89 mlxmin(-1)x1.73 m(-2) stage, the MDRD formula showed the smallest difference compared with other equations. All equations overestimated GFR in the cases with GFR < 60 mlxmin(-1)x1.73 m(-2) stages. The MDRD formula had a greater accuracy within 50% of mGFR than the equations based on cystatin C in diabetic patients. Perkins formula showed a large positive bias and low accuracy, therefore it may not be suitable for assessing GFR in patients with CKD and diabetes.</p><p><b>CONCLUSIONS</b>The formulae for estimating GFR based on cystatin C or creatinine have different trends and accuracies in patients with CKD and diabetes, especially in patients with various GFR levels. The equations based on cystatin C provide less accurate results than MDRD formulae, at least in the diabetic patients. Therefore, whether the formulae based on cystatin C are superior to MDRD formula requires further investigation in large diverse populations.</p>

Evaluation of the glomerular filtration function in type 2 diabetic patients / 中华检验医学杂志

Objective To evaluate the value of serum creatinine(Scr),creatinine clearance (Ccr),MDRD equation 7(MDRD 7),~(99)Tc~m-DTPA renal dynamic imaging(gGFR)and cystatin C in screening changed glomerular filtration function in type 2 diabetic patients.Methods The ~(99)Tc~m-Diethylene Triamine Pentaacetic Acid(~(99)Tc~m-DTPA)plasma clearance(rGFR)obtained with the dual plasma sampling method was used as a reference with which Scr,Ccr,MDRD 7,gGFR and Cystatin C were compared.Results Sixty of type 2 diabetic patients were selected,including 35 male and 25 female.The average age was(62.4?11.7)years and the average diabetic history was(10.66?9.35)years.Scr,Ccr, MDRD 7,gGFR were all correlated significantly with rGFR.Correlation coefficients were 0.675 for Ccr, -0.588 for Cystatin C,-0.500 for Scr,O.428 for MDRD 7,0.367 for gGFR(P values all