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Psychiatric Genetics Jun 2024Intellectual disability is characterized by impairment in at least two of the following areas: social skills, communication skills, self-care tasks, and academic skills....
Intellectual disability is characterized by impairment in at least two of the following areas: social skills, communication skills, self-care tasks, and academic skills. These impairments are evaluated in relation to the expected standards based on the individual's age and cultural levels. Additionally, intellectual disability is typically defined by a measurable level of intellectual functioning, represented by an intelligence quotients core of 70 or below. Autism spectrum disorder is a developmental disability resulting from differences in the brain, often characterized by problems in social communication and interaction, and limited or repetitive behaviors or interests. Hereditary spherocytosis is a disease characterized by anemia, jaundice, and splenomegaly as a result of increased tendency to hemolysis with morphological transformation of erythrocytes from biconcave disc-shaped cells with central pallor to spherocytes lacking central pallor due to hereditary injury of cellular membrane proteins. An 11-year-old female patient was referred to Pediatric Genetics Subdivision due to the presence of growth retardation and a diagnosis of hereditary spherocytosis. Since she also had dysmorphic facial features, such as frontal bossing, broad and prominent forehead, tubular nasal structure, and thin vermillion, genetic tests were performed. Chromosomal microarray analysis revealed a 2.5 Mb deletion in the 14q23.2q23.3 region. Deletion was also identified in the same region in her father, who had the same phenotypic characteristics, including hereditary spherocytosis and learning difficulties. We propose that the PLEKHG3 and AKAP5 genes, which are located in this region, may contribute to the development of intellectual disability.
Topics: Humans; Intellectual Disability; Female; Child; Haploinsufficiency; Chromosome Deletion; A Kinase Anchor Proteins; Spherocytosis, Hereditary
PubMed: 38690958
DOI: 10.1097/YPG.0000000000000368 -
Frontiers in Genetics 2024The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. We...
The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent experiments. Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. studies indicated a reduced expression of the gene. The novel c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor.
PubMed: 38655052
DOI: 10.3389/fgene.2024.1390924 -
Frontiers in Pediatrics 2024
PubMed: 38633330
DOI: 10.3389/fped.2024.1403651 -
Heliyon Apr 2024The study examined the potential of Silymarin, a blend of bioactive flavonolignans extracted from the milk thistle Silybum marianum, to mitigate Deltamethrin-induced...
The study examined the potential of Silymarin, a blend of bioactive flavonolignans extracted from the milk thistle Silybum marianum, to mitigate Deltamethrin-induced toxicity in the blood of . Fish were exposed to Deltamethrin (0.66 μg/L), the plant extract, or a combination of both for a duration of thirty days. Various parameters, including serum biochemical markers, erythrocytic abnormalities, and genotoxicity endpoints, were assessed. Results indicated a significant (p < 0.05) increase in the levels of AST, ALT, ALP, blood urea nitrogen, creatinine, glucose, cholesterol, and TLC in the fish exposed to the pesticide. Conversely, total protein, TEC, and Hb showed a notable decrease. There was also a notable rise in micronuclei and erythrocytic abnormalities such as acanthocytes, microcytes, and notched cells. Under ultrastructural examination, phenotypic deformities like spherocytosis, discocytes, and clumped erythrocytes were observed. However, dietary supplementation of silymarin (1 g/kg) significantly restored the biochemical, genetic, and cellular parameters, resembling those of the control group. This suggests the potential of this plant extract in protecting the common carp, from Deltamethrin-induced damage by scavenging free radicals and reducing DNA oxidative stress.
PubMed: 38590886
DOI: 10.1016/j.heliyon.2024.e28419 -
Cureus Mar 2024This case report presents a rare and intriguing clinical scenario involving a 63-year-old male with recurrent left-sided hydroureteronephrosis, hypertension, and...
This case report presents a rare and intriguing clinical scenario involving a 63-year-old male with recurrent left-sided hydroureteronephrosis, hypertension, and hyperlipidemia presenting with fatigue, dyspnea, and weight loss. Laboratory findings revealed anemia, basophilic stippling, spherocytosis, and nucleated red blood cells on the peripheral blood smear, raising concerns for hemolysis. Concomitant iron deficiency anemia led to further investigations, revealing gastritis and a colonic mass. A CT scan revealed splenomegaly with an accessory spleen. The histopathological evaluation identified splenic marginal zone lymphoma (MZL) - a diagnosis supported by flow cytometry. Simultaneously, the patient was found to have a moderately differentiated colorectal adenocarcinoma on colonoscopy. This unique case highlights a rare synchronous occurrence of invasive colonic adenocarcinoma with splenule MZL, an unprecedented finding in medical literature.
PubMed: 38590505
DOI: 10.7759/cureus.55843 -
British Journal of Haematology May 2024
Topics: Humans; Spherocytosis, Hereditary; Splenectomy; Male; Female; Adult; Erythrocytes; Erythrocyte Aging; Cellular Senescence; Adolescent; Middle Aged
PubMed: 38563320
DOI: 10.1111/bjh.19444 -
International Cancer Conference Journal Apr 2024A 7-year-old girl with a history of splenectomy for hereditary spherocytosis (HS) was diagnosed with renal hematoma after a blunt abdominal trauma while receiving...
A 7-year-old girl with a history of splenectomy for hereditary spherocytosis (HS) was diagnosed with renal hematoma after a blunt abdominal trauma while receiving aspirin. Multiple erythrocyte transfusions and transarterial embolization were performed without success. Eventual nephrectomy revealed severely necrotic and perforated Stage III Wilms tumor (WT). Radiochemotherapy was administered, but by the eighth week, she developed severe hepatic sinusoidal obstruction syndrome (HSOS). Her ferritin level at the time was 3406 ng/ml. Defibrotide and aggressive supportive measures provided full recovery. The patient was given deferasirox for iron chelation therapy and finished her treatment without incident. To our knowledge, just one patient with HS and WT has been described in the literature. The role of iron excess in HSOS pathogenesis in non-transplant patients has not been addressed before either. Transfusional hyperferritinemia, in addition to chemotherapeutics and radiation, may have contributed to the development of severe HSOS in our patient.
PubMed: 38524657
DOI: 10.1007/s13691-023-00641-7 -
Clinical Journal of Gastroenterology Mar 2024A 6-year-old girl previously diagnosed with hereditary spherocytosis was admitted to our hospital with gallstones and cholangitis. Endoscopic retrograde...
A 6-year-old girl previously diagnosed with hereditary spherocytosis was admitted to our hospital with gallstones and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed, and fluoroscopy revealed a dilated common bile duct (CBD) without evident stones, possibly due to spontaneous excretion through the papilla of Vater. A 7-French plastic stent was inserted into the CBD. After the procedure, a marked increase in pancreatic enzyme levels was observed, and she was diagnosed with post-ERCP pancreatitis (PEP). Stent placement could have been a cause of pancreatitis; therefore, we removed the stent. Subsequently, recovery from pancreatitis was confirmed, although she suddenly complained of abdominal pain and was diagnosed with choledocholithiasis recurrence. ERCP was repeated, and fluoroscopy revealed a dilated CBD with a stone. A minimal endoscopic sphincterotomy (EST) was performed to reduce the risk of PEP, and a biliary dilation balloon placed across the papilla was gradually inflated until the waist of the balloon disappeared. Stones were extracted using a retrieval balloon catheter. The abdominal pain resolved immediately, and the patient recovered without developing PEP. To our knowledge, this is the first case report of a pediatric patient treated with minimal EST followed by papillary balloon dilation for choledocholithiasis.
PubMed: 38517593
DOI: 10.1007/s12328-024-01960-9 -
EMBO Reports Apr 2024Stop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a...
Stop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a transcript-selective manner using a CRISPR-dCas13 system. Using specific guide RNAs, we target dCas13 to the region downstream of canonical stop codons of mammalian AGO1 and VEGFA mRNAs, known to exhibit natural SCR. Readthrough assays reveal enhanced SCR of these mRNAs (both exogenous and endogenous) caused by the dCas13-gRNA complexes. This effect is associated with ribosomal pausing, which has been reported for several SCR events. Our data show that CRISPR-dCas13 can also induce SCR across premature termination codons (PTCs) in the mRNAs of green fluorescent protein and TP53. We demonstrate the utility of this strategy in the induction of readthrough across the thalassemia-causing PTC in HBB mRNA and hereditary spherocytosis-causing PTC in SPTA1 mRNA. Thus, CRISPR-dCas13 can be programmed to enhance or induce SCR in a transcript-selective and stop codon-specific manner.
Topics: Animals; Codon, Terminator; Clustered Regularly Interspaced Short Palindromic Repeats; RNA, Guide, CRISPR-Cas Systems; Codon, Nonsense; RNA, Messenger; Protein Biosynthesis; Mammals
PubMed: 38499809
DOI: 10.1038/s44319-024-00115-8 -
Annals of Medicine and Surgery (2012) Mar 2024Hereditary spherocytosis (HS), a rare familial extravascular haemolytic disorder, typically follows an autosomal dominant inheritance pattern with variable expressivity....
INTRODUCTION AND IMPORTANCE
Hereditary spherocytosis (HS), a rare familial extravascular haemolytic disorder, typically follows an autosomal dominant inheritance pattern with variable expressivity. Despite its classical presentation of anaemia, jaundice, and splenomegaly, HS is infrequently reported among individuals of Asian descent, contributing to its under diagnosis or delayed diagnosis. The primary objective of this case report is to underscore the pivotal role of the osmotic fragility test in diagnosing HS, emphasizing the importance of accurate and timely identification for effective clinical management and improved patient outcomes.
CASE PRESENTATION
The patient, without known prior co-morbidities, presented with recurrent abdominal distension, early satiety, and easy fatigability persisting for 6 years. Physical examination revealed icterus, gnathopathy, left hypochondrium tenderness, and palpable splenomegaly. The osmotic fragility of red cells was significantly elevated. The patient underwent optimization before splenectomy, receiving immunization against encapsulated bacteria. Packed red blood cell transfusions were administered to achieve optimal haemoglobin levels. Follow-up showed symptom relief, significantly improving the patient's quality of life.
CLINICAL DISCUSSION
This case underscores the challenges of delayed HS diagnosis, with the patient enduring symptoms for years before seeking appropriate medical attention. Overlooking the simplicity and cost-effectiveness of an osmotic fragility test prolonged the diagnostic journey, emphasizing the impact on overall well-being.
CONCLUSION
HS remains underdiagnosed, especially in our regions. The osmotic fragility test emerges as an economical diagnostic tool in resource-limited settings, particularly when spherocytosis is absent in the peripheral blood smears. Its inclusion in diagnostic protocols can expedite accurate HS identification and enhance patient outcomes.
PubMed: 38463107
DOI: 10.1097/MS9.0000000000001804