Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)–based haploidentical hematopoietic cell transplantation (HCT) along with a ...strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2–65) undergoing PTCy-based haploidentical HCT with (
n
= 71) or without (
n
= 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 10
4
copies/ml developed clinical symptoms (
n
= 65). The incidence of BK viruria ≥ 10
4
copies/ml was 7.1% (
n
= 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 10
4
copies/ml and HC were strongly associated with acute GVHD (
p
< 0.001). A higher NRM was observed in those with BK viruria ≥ 10
4
copies/ml, related to GVHD and its complications (41.7% vs 12.6%,
p
= 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 10
4
copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.
Background
Tibial muscular dystrophy (TMD), tardive, is a dominantly inherited mild degenerative disorder of anterior tibial muscles. Mutations of
Titin (TTN)
have been reported in patients with ...different phenotypes such as skeletal muscular abnormalities or complex overlapping disorders of muscles.
Titin
(
TTN
) is a large 363 exon gene that encodes an abundant protein (the longest polypeptide known in nature) expressed in the heart and skeletal muscles.
Methods
DNA from peripheral blood sample was extracted, whole exome sequencing (WES) was performed, and a neuromuscular disorders related gene-filtering strategy was used to analyse the disease-causing mutations. Further, sanger sequencing was applied to confirm the variant.
Results
A novel missense variant (c.41529G > C;p.Arg13843Ser) of
TTN
gene was identified in a patient with lower limb weakness, occasional tongue fasciculation and mild scoliosis. This variant leads to a substitution of arginine with serine, causing structural changes in titin protein that is responsible for the TMD disease.
Conclusion
The novel variant detected has widened the genetic spectrum of
TTN
-associated diseases, further functional studies will aid in establishing the clinical diagnosis.
Abstract
Background
The translocation t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML) sub type M2. About 3–5 % of cases with ...additional chromosomal abnormalities, including structural and numerical ones, are reported to include a complex translocation t(8;21;N).
Case presentation
Here we report a chromosome rearrangement observed in a 19 years-old female diagnosed with AML-M2. When subjected to (molecular) cytogenetic analyses a complex three-way translocation involving chromosomes 8, 17 and 21 was detected, forming not a t(8;21;17) as one would expect. Real time-polymerase chain reaction analysis using 6 AML specific markers showed the presence of
RUNX1
/
RUNX1T1
fusion gene transcripts identical to those found in classical translocation t(8;21) coupled with presence of
FLT3
-
ITD
mutation identified by fragment analysis.
Conclusions
The present case highlights importance of complex rearrangements rarely encountered in AML, suggesting that all involved regions harbor critical candidate genes regulating the pathogenesis of AML, leading to novel as well as well-known leukemia associated chromosomal aberrations.
Background
Alagille syndrome is an autosomal dominant disorder associated with variable clinical phenotypic features including cholestasis, congenital heart defects, vertebral defects, and dysmorphic ...facies.
Objective
Whole exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new possibilities for mutations or genes identification.
Methods
WES was used to identify pathogenic variants, which may have significant prognostic implications for patients’ clinical presentation of the proband. In this paper, we have uncovered a novel JAGGED1 gene (JAG1) mutation associated with Alagille syndrome in a 5-year-old girl presented with conjugated hyperbilirubinemia and infantile cholestasis.
Results
The exome sequencing analysis revealed the presence of a novel JAG1 heterozygous c.3080delC variant in exon 25. The detected variant introduced a stop codon (p.P1027RfsTer9) in the gene sequence, encoding a truncated protein. Our exome observations were confirmed through Sanger sequencing as well.
Conclusions
Here, we report a case of a patient diagnosed with Alagille syndrome, conjugated hyperbilirubinemia, and infantile cholestasis, with emphasis on its association with the detection of the novel JAG1 mutation, thereby establishing the genetic diagnosis of the disease.
Direct Acting Antivirals (DAA) have changed the landscape of hepatitis C virus (HCV) infection with high cure rates across genotypes. However, the use of these agents in the setting of allogeneic ...hematopoietic cell transplantation (HCT) has been limited. In this context, we report the outcome of five children (5‐12 years) with relapsed and refractory leukemia and active HCV infection (genotype 1b), who underwent urgent haploidentical HCT and were treated with Sofosbuvir and Velpatasvir (Sof‐Vel) from initiation of treatment to 24 weeks post‐HCT. All achieved complete virologic response (VR) at a median of 2 weeks, with normalization of liver enzymes. There were no adverse events related to the use of Sof‐Vel, with no major fluctuations in cyclosporine levels. Two of the patients developed chronic GVHD and one relapsed. Sof‐Vel was continued in one of them along with sirolimus without affecting drug levels. With a median follow‐up of 15 months, four patients are disease free with sustained VR. Our study shows that combination of Sof‐Vel might be effective in inducing rapid complete and sustained VR during HCT without any major untoward drug interaction.
Following a major seasonal outbreak of H1N1 influenza in 2018 September, prophylactic oseltamivir for six months was initiated in children undergoing haploidentical HCT with regular monitoring for ...influenza and other respiratory virus infections. Influenza was not detected in 22 children undergoing prophylaxis, compared to 8 H1N1 infections in 21 adults without prophylaxis (P = .01). Four children on prophylaxis were detected to have other respiratory viruses, compared to 8 in those without prophylaxis. Invasive pulmonary aspergillosis (IPA) was observed only in association with H1N1 (4/8 with H1N1 vs 0/35 without H1N1, P = .001) and was thus lower in the prophylaxis group (P = .04). The overall incidence of episodes of respiratory illness and hospital stay were also lower in those on prophylaxis (P = .001). There were no untoward side effects associated with prophylactic oseltamivir. Prophylactic oseltamivir was safe and effective in prevention of H1N1 infection and subsequent IPA in children at‐risk, early after haploidentical HCT.
Introduction
Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs.
...Background
We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma.
Conclusion
Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.
Post-transplantation cyclophosphamide (PTCy)-based HCT has been associated with an increased frequency of hemorrhagic cystitis (HC), dominantly associated with BK viruria. We prospectively evaluated ...the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65), malignant(87) and non-malignant(28), undergoing PTCy-based haploidentical HCT with CTLA4Ig (n=71) or without (n=44). Conditioning was predominantly myeloablative (74%). As prophylaxis for HC, continuous infusion of Mesna was used from 30 minutes prior to PTCy at 50% of the daily dose of Cy every 8 hourly for 72 hours. Development of HC before day+15 was termed as ‘early HC’ and later was referred to as ‘HC’.
The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n=65). The incidence of BK viruria ≥ 104 copies/ml (‘high BK viruria’) was 7.1 % (n=8) and 75% developed HC. The incidence of HC was 5.4 % at a median of 30 days. Only 3.1% (events-2/66) of patients greater than 18 years of age had high BK viruria compared to 12.4% (events-6/49) in those who were younger than 18 years (p=0.05). The overall incidence of grade 2-4 acute GVHD was 16.9% (95%CI, 13.4-20.4). Overall BK viruria was higher in those with acute GVHD (92.1% vs 60.6 in those without acute GVHD, p=0.002, Figure 1A). Acute GVHD preceded the development of high BK viruria in 7 out of 8 patients with a median onset at 22 days (14-36 days). The incidence of high BK viruria in patients with acute GVHD was 36.8% (95% CI 25.7-37.9), compared to 1.1% (95% CI 0.1-2.2) in those without acute GVHD (p=0.0001). The incidence of HC in those with acute GVHD was likewise significantly higher (26.7%; 95%CI, 16.5-36.9 vs 1.1%; 95% CI 0.1-2.2, p=0.0001, Figure 1B).
Overall BK viruria was significantly lower in those receiving CTLA4Ig (54.1% vs 89.4% in those without CTLA4Ig, p=0.001, Figure 2A). The incidences of both high BK viruria (4.3% with vs 11.9% without CTLA4Ig, p=0.08) and HC (2.9% with vs 9.5% without CTLA4Ig p=0.09, Figure 2B) tended to be lower in those receiving CTLA4Ig-based protocols. A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p=0.04).
In conclusion, our study demonstrates that extended infusion of Mesna, along with reduction in alloreactivity with the use of CTLA4Ig were probably responsible for a much lower incidence of BK viruria and resultant HC, than previously reported following PTCy-based haploidentical HCT.
Cyclodextrin glucanotransferase (CGTase) is a commercially important enzyme which catalyses the formation of cyclodextrins (CDs) from starch. A CGTase producing bacterium was isolated from soil which ...gave a fairly high enzyme activity of 7.5 U ml
1
after 24 h of growth which was further increased to 22 U ml
1
by proper media design. The enzyme was purified to homogeneity by a novel single affinity precipitation step which resulted in a very high recovery of more than 90%. The molecular weight, as determined by SDS-PAGE, was found to be 68 kDa. The pH optimum was found to be 6.6 while a temperature optimum of 65�C was observed. The enzyme exhibited a fairly high degree of functional stability with little loss of activity, even after 8 h of incubation at 65�C. Ca
++
had little effect on the activity of the enzyme while urea at 10 mM concentration increased the activity of the enzyme by more than 200%, suggesting that it is a unique enzyme
PDF
