Effect of combined NPHS2 and ACTN4 variants in the onset and severity of focal segmental glomerulosclerosis
Michelle T. Passos1, Patricia Varela2, Danilo E. Fernandes1, M. Goretti Polito1, João B. Pesquero2#, Gianna Mastroianni Kirsztajn1#*
1Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil
2Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil
#Both authors had equal participation in this study and share senior authorship
Introduction: Focal segmental glomerulosclerosis (FSGS) can be caused by mutations in the genes NPHS2, ACTN4, TRPC6, and INF2 among others, presenting variable levels of proteinuria, including nephrotic syndrome, that frequently progress to end-stage renal disease (ESRD). The establishment of the genotype-phenotype correlation caused by mutations in genes expressed in the podocyte could contribute to understanding their role in FSGS and to the decision-making in the clinical setting in similar cases.
Methods: Genomic DNA was extracted from peripheral blood of the proband, his brother, sister and mother. All the exons of the genes NPHS2, ACTN4, TRPC6, and INF2 were amplified by a polymerase chain reaction, purified, and sequenced by the Sanger method. The presence of variants was evaluated in the proband with FSGS and relatives, reviewed, and annotated using dbSNP and HGMD.
Results: In the clinical evaluation, the proband and his brother presented childhood-onset nephrotic syndrome, added with renal biopsies confirming FSGS, which was resistant to steroid and other immunosuppressive drugs, and progressed to ESRD. Both patients showed the variants p.P316S in NPHS2 and p.G894S in ACTN4, as well as the polymorphism p.R229Q in NPHS2, all variants in heterozygosis. Their parents were healthy, and the mother presented only the variant p.P316S in NPHS2 in heterozygosis.
Conclusions: The family members with FSGS had a combination of the variants p.P316S and p.R229Q in NPHS2, and p.G894S in ACTN4, shared similar clinical presentation, nephrotic syndrome with onset in late childhood that rapidly progressed to ESRD.DOI: 10.29245/2572-9411/2022/1.1205 View / Download Pdf
Bhumika Dua, Rajaram Sharma*, Tapendra N. Tiwari, Saurabh Goyal
Department of Radio-Diagnosis, Pacific Institute of Medical Sciences, Umarda, Udaipur, Rajasthan, India
For the past few decades, a solid mass in the kidney with avid enhancement was considered renal cell carcinoma (RCC). With the advancement in radiological interventions, the understanding and treatment of a large number of tumours has changed. Oncocytomas are solid benign renal masses contributing 3-7% in all renal neoplasms. We report a case of a 32-year-old male who presented to our medicine OPD with abdominal pain and discomfort for about one month, later diagnosed with oncocytoma. We emphasize the importance of the typical imaging findings for the diagnosis and characterization of renal tumors.DOI: https://doi.org/10.29245/2572-9411/2022/1.1203 View / Download Pdf
DOI: 10.29245/2572-9411/2021/2.1202 View / Download Pdf
Moustapha Niasse1*, Awa Cheikh Ndao2, Ramadhane Bouchrane1, Siddiki Charifah1, Adama Bah1, Saïdou Diallo1
1Department of Rheumatology, University Hospital Aristide Le Dantec of Dakar, Senegal
2Department of Internal Medicine, University Hospital Aristide Le Dantec of Dakar, Senegal
Mona Al Mukaddam1, Kin Cheung2, Sammi Kile3, Michelle Davis3, Frederick S. Kaplan1,4 Robert J. Pignolo5*
1Departments of Medicine, Orthopaedic Surgery, and The Center for Research in FOP and Related Disorders, The Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA
2BioSAS Consulting, Inc., Wellesley, Massachusetts, USA
3International FOP Association (IFOPA), North Kansas City, Missouri, USA
4Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine
5Chair, Geriatric Medicine & Gerontology, Robert and Arlene Kogod Professor of Geriatric Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
Background:Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease characterized by malformed great toes and progressive heterotopic ossification (HO) in soft tissues. Current standard-of-care is aimed at palliation of symptoms; there are no currently approved therapies to prevent HO. Recurrent episodes of HO starting in early life lead to cumulative disability, severe functional limitations, and shortened life span. Most individuals require assistive devices and extensive caregiver support before the second decade of life. Caregiver support is thought to be high, but the timing and extent of caregiver support in FOP has not been formally assessed. Methods: Using data from the International FOP Association (IFOPA) Global Registry on 299 patients (median age 21 years; range 0.1 to 78 years) from 54 countries, we characterized the extent of caregiver support by assessing the number of part-time and full-time caregivers and school aides reported by participants, based on age. Results: Over 50% of FOP Registry respondents reported a need for part-time or full-time home personal care attendants. The percentage of individuals who reported a requirement for bathing attendants and part- or full-time home personal care attendants increased with age (>1 part-time or full-time caregiver exceeded 30% for individuals >15 years of age), as did the number of part-time or full-time attendants. Support from school aides peaked between 9 and 15 years of age. Conclusion: Caregiver support in FOP is high in terms of time and amount of support needed, increases rapidly with age, and is substantial by the second decade of life. These findings highlight the urgent need for transformative treatments that will preserve the independence of individuals with FOP.DOI: 10.29245/2572-9411/2021/1.1200 View / Download Pdf
Clinical and laboratory features that differentiate familial from sporadic focal segmental glomerulosclerosis in adolescents and adults
Maria Goretti Polito1, Michelle Tiveron Passos1, Danilo Euclides Fernandes1, Gianna Mastroianni-Kirsztajn2*
1Department of Medicine (Nephrology), Federal University of São Paulo, São Paulo-SP, Brazil
2Associate Professor of Medicine, Department of Medicine (Nephrology), Federal University of São Paulo, São Paulo-SP, Brazil
Background: Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease in children and adults. Although most cases are sporadic (s), familial (f) presentation is also described. The purpose of the present study was to establish clinical and laboratory profiles of fFSGS vs. primary sFSGS, contributing to the distinguishing diagnosis in clinical practice and best management, in particular when mutation analysis is not available.
Methods: Demographic, clinical and laboratorial parameters were studied in 124 patients 12 years and older with FSGS, subdivided in sFSGS (n=89) and fFSGS (n=35).
Results: General and clinical features were similar, as well as serum creatinine at disease presentation. Proteinuria levels were more frequently ≥ 3g/day in sFSGS (63.8%) than in fFSGS (44%, p=0.080), and serum albumin levels were < 3.0 g/dL in 45.8% and 20%, respectively (p=0.046). The groups were statistically different regarding steroid resistance, corresponding to 60% in sFSGS and 100% in fFSGS (p=0.001).
Conclusions: The studied groups were clinically similar, except that proteinuria tended to be higher (nephrotic range) and serum albumin was lower in sFSGS vs. fFSGS. In addition, all treated fFSGS patients were steroid resistant. At presentation it is important to characterize if the patient has fFSGS, that will contribute to further disease management, and disease history will be the first clue for such differential diagnosis.