Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2.

BACKGROUND: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations). AIM: To study the mutation spectrum in ICF syndrome. MATERIALS AND METHODS: Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members. RESULTS: We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta-analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients. DISCUSSION: The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort. CONCLUSION: Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes.

Clinical outcomes of acute kidney injury developing outside the hospital in elderly.

PURPOSE: Although various studies have improved our knowledge about the clinical features and outcomes of acute kidney injury developing in the hospital (AKI-DI) in elderly subjects, data about acute kidney injury developing outside the hospital (AKI-DO) in elderly patients (age ≥ 65 years) are still extremely limited. This study was performed to investigate prevalence, clinical outcomes, hospital cost and related factors of AKI-DO in elderly and very elderly patients. METHODS: We conducted a prospective, observational study in patients (aged ≥ 65 years) who were admitted to our center between May 01, 2012, and May 01, 2013. Subjects with AKI-DO were divided into two groups as "elderly" (group 1, 65-75 years old) and "very elderly" (group 2, >75 years old). Control group (group 3) consisted of the hospitalized patients aged 65 years and older with normal serum creatinine level. In-hospital outcomes and 6-month outcomes were recorded. Rehospitalization rate within 6 months of discharge was noted. Hospital costs and mortality rates of each group were investigated. Risk factors for AKI-DO were determined. RESULTS: The incidence of AKI-DO that required hospitalization in elderly and very elderly patients was 5.8 % (136/2324) and 11 % (100/905), respectively (p < 0.001), with an overall incidence of 7.3 % (236/3229). Chronic kidney disease (CKD) was developed in 43.4 % of group 1 and 67 % of group 2 within the 6 months of discharge (p < 0.001). Progression to CKD was significantly lower in the control group than in groups 1 and 2 (p < 0.001). Mortality rates for groups 1, 2 and 3 were 23.5 % (n = 32), 31 % (n = 31) and 4.2 % (n = 8), respectively (p < 0.05). Rehospitalization rate within the 6 months of discharge for the groups with AKI-DO was higher than for the control group (p < 0.001). Hospital cost of groups 1 and 2 was significantly higher than that of the control group (p < 0.001). Nonsteroidal anti-inflammatory drugs (NSAIDs) (OR: 6.839, 95 % CI = 4.392-10.648), angiotensin-converting enzyme inhibitors (ACEI) (OR: 7.846, 95 % CI = 5.161-11.928), angiotensin receptor blockers (ARB) (OR: 6.466, 95 % CI = 4.813-8.917), radiocontrast agents (OR: 8.850, 95 % CI = 5.857-13.372), hypertension (OR: 4.244, 95 % CI = 2.729-6.600), diabetes mellitus (OR: 2.303, 95 % CI = 1.411-3.761), heart failure (OR: 3.647, 95 % CI = 2.276-5.844) and presence of infection (OR: 3.149, 95 % CI = 1.696-5.845) were found as the risk factors for AKI-DO in elderly patients (p < 0.001 for all). Patients with AKI-DO had higher 6-month mortality rate (HR 1.721, 95 % CI: 1.451-2.043, p < 0.001). Mortality risk increased 0.519 times at 20th day. CONCLUSIONS: The incidence of AKI-DO requiring hospitalization is higher in very elderly patients than elderly ones, especially in male gender. Use of ACEI, ARB, NSAID and radiocontrast agents is the main risk factors for the development of AKI-DO in the elderly.

Pure red cell aplasia preceding malignant lymphoma in a renal transplant patient.

Malignant disorders are one of the major causes of morbidity and mortality in transplant patients. We present herein a renal transplant recipient with malignant lymphoma which preceded by pure red cell aplasia (PRCA). Acquired PRCA is a rare hematologic disorder in renal transplant recipients. It has been associated with a variety of disorders of immunologic dysfunction and neoplasms, exposure to drugs and toxins, infectious diseases, pregnancy and severe nutritional deficiency. This is the first case with PRCA preceding the malign lymphoma in a renal transplant patient. Treatment of lymphoma and lymphoma-related humoral and cellular changes or other undefined effects that may be related to therapy may be responsible of the resolving of PRCA in this patient. In this regard, renal transplant patients with acquired PRCA, must be closely followed for an underlying neoplastic disorder.