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Cureus Jun 2024Multiple myeloma (MM) immunophenotyping (IPT) and measurable residual disease (MRD) monitoring by flow cytometry is a surrogate for progression-free survival and overall...
BACKGROUND
Multiple myeloma (MM) immunophenotyping (IPT) and measurable residual disease (MRD) monitoring by flow cytometry is a surrogate for progression-free survival and overall survival in clinical trials. However, plasma cell enumeration is challenging owing to morphological discrepancies and plasma cell (PC) loss during the sample processing.
METHODS
In (n=87) newly diagnosed MM patients, we evaluated the immunophenotype of PCs at baseline, and for a subset of 35 patients MRD at post-induction was quantified and analyzed for association with outcomes and survival. The software Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc., Chicago, IL, USA) was used for all the statistical analysis.
RESULTS
Immunophenotyping showed strong positive expression of CD56 (83%), CD200 (94%), CD38 (92%), and CD117 (91%) and negative/weak expression of CD19 (83%), CD45 (89%), CD27 (74%), and CD81 (90%) respectively. Negative/weak expression of CD19 was significantly associated with age ≥56 years (p<0.048), with lower albumin (<3.4g/dL, p<0.001). Strong positive CD56 expression was significantly associated with the presence of M-protein (p<0.03). Strong positive CD117 expression was significantly associated with lower albumin (p<0.02). Strong positive CD200 expression was significantly associated with a good response (p<0.02). The median (IQR) value of bone marrow (BM)-MRD% was 0.005 (0.002-0.034). We found that there was no significant difference in the correlation, association, and survival outcomes with MRD%.
CONCLUSION
This study sheds light on the utility of IPT as an invaluable diagnostic tool in disease management. The findings of this study could be important when it comes to modifying the criteria for high-risk diseases and implementing a risk-adapted first therapy in clinical practice.
PubMed: 38952609
DOI: 10.7759/cureus.61504 -
Frontiers in Oncology 2024Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests...
BACKGROUND
Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests that within this expansive family, the EphA subset is implicated in driving cancer cell progression, proliferation, invasion, and metastasis, making it a promising target for anticancer treatment. Nonetheless, the extent of EphA family involvement across diverse cancers, along with its intricate interplay with immunity and the tumor microenvironment (TME), remains to be fully illuminated.
METHODS
The relationships between EphA gene expression and patient survival, immunological subtypes, and TME characteristics were investigated based on The Cancer Genome Atlas (TCGA) database. The analyses employed various R packages.
RESULTS
A significant difference in expression was identified for most EphA genes when comparing cancer tissues and non-cancer tissues. These genes independently functioned as prognostic factors spanning multiple cancer types. Moreover, a significant correlation surfaced between EphA gene expression and immune subtypes, except for EphA5, EphA6, and EphA8. EphA3 independently influenced the prognosis of papillary renal cell carcinoma (KIRP). This particular gene exhibited links with immune infiltration subtypes and clinicopathologic parameters, holding promise as a valuable biomarker for predicting prognosis and responsiveness to immunotherapy in patients with KIRP.
CONCLUSION
By meticulously scrutinizing the panorama of EphA genes in a spectrum of cancers, this study supplemented a complete map of the effect of EphA family in Pan-cancer and suggested that EphA family may be a potential target for cancer therapy.
PubMed: 38952552
DOI: 10.3389/fonc.2024.1378087 -
Heliyon Jun 2024The present study was carried out at the Plant Pathology Hafizabad Research Station, the University of Layyah, during the crop seasons 2021-2022 and 2022-2023 to...
The present study was carried out at the Plant Pathology Hafizabad Research Station, the University of Layyah, during the crop seasons 2021-2022 and 2022-2023 to evaluate the response of various wheat genotypes against leaf rust severity (%), environmental conditions favourable for disease development and grain yield. Except for minimum temperature and minimum relative humidity, which had a negative association with disease development, there was a significant correlation between leaf rust severity (%) and all environmental conditions such as maximum temperature, maximum relative humidity, rainfall, and wind speed. All epidemiological variables such as maximum temperature, minimum temperature, minimum relative humidity, rainfall and wind speed significantly affect the disease progression. The disease predictive model accounted for 48-69 % variability in leaf rust severity. The model performance was evaluated using the coefficient of determination (R = 0.69) and RMSE, both demonstrated acceptable predictive results for leaf rust severity (%) management. Leaf rust severity (%) increased with an increase in maximum temperature (17.8-30 °C), maximum relative humidity (76.3-85 %), rainfall (2.2-10.85 mm) and wind speed 1.1-2.7 km/h and decreased with the increase of minimum temperature (7.91-16.71 °C) minimum relative humidity (47.15-56.45 %) during both rating seasons 2021-2022 and 2022-2023. The single and two applications of fungicides at the Zadok's scale 3, ZS 4.3, and ZS 5.4 stages led to a significant reduction in grain yield losses caused by leaf rust severity (%) in both the 2021-2022 and 2022-2023 crop seasons. Single and two sprays of prothioconazole, were found to be the first choice among all treatments to reduce the disease severity and increase grain production and maximum gross revenue (513.1-777.8$/ha), as compared to followed by single and two sprays of propiconazole (Progress), tebuconazole + trifloxystrobin, tebuconazole, bixafen + tebuconazole, and propiconazole (Tilt), respectively. These findings recommend the involvement of genotype resistance and weather predictors in wheat leaf rust development, along with fungicide application studies, to improve the predictability of host resistance to disease, future models, and the sustainability of disease control methods.
PubMed: 38952372
DOI: 10.1016/j.heliyon.2024.e32564 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jun 2024To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal...
OBJECTIVE
To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by infection, and to examine the effect of oxymatrine (OMT) on in mice.
METHODS
Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 10 oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of , , , myeloid differentiation primary response gene 88 () and was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay.
RESULTS
HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height ( = 6.207, = 0.000 5), intestinal crypt depth ( = 6.903, = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth ( = 37.190, < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; = 4.178, < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; = 3.130, < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] ( = 3.877, < 0.01) and GA group [(143.3 ± 24.7) μm] ( = 2.710, < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group ( = 3.888, < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group ( = 1.989, > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group ( = 4.133, < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group ( = 0.575, > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) ( = 10.540, < 0.01) and the GA group (2.7 ± 0.3) ( = 7.370, < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group ( = 15.020, < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group ( = 0.404, > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin ( = 28.031, < 0.000 1) and ZO1 expression ( = 14.122, < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; = 3.810, < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group ( = 7.620 and 5.391, both values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group ( = 1.791 and 2.033, both values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; = 4.485, < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] ( = 5.159, < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] ( = 4.441, < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group ( = 0.037 and 0.742, both values > 0.05). qPCR assay showed significant differences among the four groups in terms of ( = 21.980, < 0.000 1), ( = 20.630, < 0.000 1), ( = 17.000, = 0.000 6), ( = 8.907, = 0.000 5) and expression in mouse jejunal tissues ( = 8.889, = 0.000 7). The relative expression of [(5.97 ± 1.07) vs. (1.05 ± 0.07); = 6.482, < 0.05] 、 [(5.92 ± 1.29) vs. (1.10 ± 0.14); = 5.272, < 0.05] 、 [(5.96 ± 1.50) vs. (1.02 ± 0.03); = 4.644, < 0.05] 、 [(3.00 ± 1.26) vs. (1.02 ± 0.05); = 2.734, < 0.05] and [(2.33 ± 0.72) vs. (1.04 ± 0.06); = 2.665, < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of (0.63 ± 0.01), (0.42 ± 0.10), (0.35 ± 0.07), (0.70 ± 0.11) and (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group ( = 8.629, 5.830, 11.500, 4.729 and 6.898, all values < 0.05), and the relative expression of , , , and significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group ( = 7.052, 6.035, 4.084, 3.165 and 3.274, all values < 0.05). In addition, the relative expression of (1.14 ± 0.60), (1.00 ± 0.24), (1.14 ± 0.07), (0.96 ± 0.25) and N (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group ( = 7.059, 5.320, 3.510, 3.466 and 3.273, all values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of , , , or in mouse jejunal tissues ( = 0.239, 0.518, 1.887, 0.427 and 0.641, all values > 0.05).
CONCLUSIONS
infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.
Topics: Animals; Cryptosporidiosis; Quinolizines; Mice, Inbred BALB C; Cryptosporidium parvum; Toll-Like Receptor 4; Mice; Toll-Like Receptor 2; NF-kappa B; Alkaloids; HMGB1 Protein; Signal Transduction; Male; Intestinal Mucosa; Matrines
PubMed: 38952315
DOI: 10.16250/j.32.1374.2024019 -
Archives of Pathology & Laboratory... Jul 2024In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and...
CONTEXT.—
In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications.
OBJECTIVE.—
To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States.
DESIGN.—
An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media.
RESULTS.—
A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas.
CONCLUSIONS.—
Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.
PubMed: 38952288
DOI: 10.5858/arpa.2024-0031-OA -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A...
Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A comprehensive analysis was conducted using various online databases to assess the mRNA and protein expression of NUP85 in HCC, as well as its mutation status and prognostic diagnostic value. The immune relevance of NUP85 was evaluated using single-cell sequencing data and resources from the Tumor Immune Estimation Resource (TIMER) and the Gene Expression Profiling Interactive Analysis 2021 (GEPIA2021) databases. The drug sensitivity of NUP85 was analyzed through the Genomic Landscape of Cancer (GSCA) and the Clinical Bioinformatics Home. Co-expressed genes of NUP85 in HCC were filtered using the Hepatocellular Carcinoma Comprehensive Molecular Database (HCCDB), and the correlation between NUP85 and its related genes was analyzed using the R language "limma" package. The gene ontology (GO) functions, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) of NUP85 and its related genes were performed using the R language "clusterProfiler" package. The Clinical Bioinformatics Home was utilized to construct heatmaps and prognostic risk scoring models for NUP85 and its related genes. Results NUP85 mRNA and protein expression were upregulated in HCC, showing high levels across dif-ferent stages and grades, which indicates a poor prognosis for patients. The mutation rate of NUP85 in HCC samples was 19%, significantly affecting the overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of patients. NUP85 was highly expressed in various immune cells, including macrophages, B cells, and T cells, and was positively correlated with the infiltration levels of multiple immune cells. The expression of NUP85 was significantly correlated with multiple drugs, such as Milademetan (PD0325901), a structural analog of Vemurafenib (PLX4720), and Regorafenib (PD0325901). The GO functions of NUP85 and its co-expressed genes were mainly enriched in organelle fission, nuclear division, and chromosome segregation, while the KEGG pathways were primarily enriched in the cell cycle and kinesin proteins. These factors significantly and unfavorably affected the OS of HCC patients, and the areas under the ROC curve (AUC) for the 1-year, 3-year, and 5-year OS prognostic diagnosis of HCC patients were all greater than 0.7. Conclusion The high expression of NUP85 in HCC is correlated with a poor prognosis and is related to various immune cells and drugs, making it a potential biomarker for di-agnosis, treatment, and prognosis in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Nuclear Pore Complex Proteins; Prognosis; Gene Expression Regulation, Neoplastic; Male
PubMed: 38952090
DOI: No ID Found -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis....
Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis. Methods Gene expression datasets from GEO (GSE30528, GSE30529) and RNA sequencing (RNA-seq) data from the Karolinska Kidney Research Center were used. Gene set enrichment analysis (GSEA) was conducted to examine differences in immune-related gene expression in the glomeruli and tubules (DKD) patients. To identify immune-related genes (IRGs) and TFs, differential expression analysis was carried out using the Limma and DESeq2 software packages. Key immune-related TFs were pinpointed through co-expression analysis. The interaction network between TFs and IRGs was constructed using the STRING database and Cytoscape software. Furthermore, the Nephroseq database was employed to investigate the correlation between the identified TFs and clinical-pathological features. Results When compared to normal control tissues, significant differences in the expression of immune genes were observed in both the glomeruli and tubules of individuals with Diabetic Kidney Disease (DKD). Through differential and co-expression analysis, 50 immune genes and 9 immune-related transcription factors (TFs) were identified in the glomeruli. In contrast, 131 immune response genes (IRGs) and 41 immune-related TFs were discovered in the renal tubules. The protein-protein interaction (PPI) network highlighted four key immune-related TFs for the glomeruli: Interferon regulatory factor 8 (IRF8), lactotransferrin (LTF), CCAAT/enhancer binding protein alpha (CEBPA), and Runt-related transcription factor 3 (RUNX3). For the renal tubules, the key immune-related TFs were FBJ murine osteosarcoma viral oncogene homolog B (FOSB), nuclear receptor subfamily 4 group A member 1 (NR4A1), IRF8, and signal transducer and activator of transcription 1 (STAT1). These identified TFs demonstrated a significant correlation with the glomerular filtration rate (GFR), highlighting their potential importance in the pathology of DKD. Conclusion Bioinformatics analysis identifies potential genes associated with DKD pathogenesis and immune dysregulation. Further validation of the expression and function of these genes may contribute to immune-based therapeutic research for DKD.
Topics: Humans; Diabetic Nephropathies; Transcription Factors; Computational Biology; Gene Expression Profiling; Kidney Glomerulus; Gene Regulatory Networks; Kidney Tubules
PubMed: 38952087
DOI: No ID Found -
Advanced Science (Weinheim,... Jul 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks,...
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.
PubMed: 38952069
DOI: 10.1002/advs.202404326 -
British Journal of Pharmacology Jul 2024The vascular endothelium dynamically responds to environmental cues and plays a pivotal role in maintaining vascular homeostasis by regulating vasomotor tone, blood cell... (Review)
Review
The vascular endothelium dynamically responds to environmental cues and plays a pivotal role in maintaining vascular homeostasis by regulating vasomotor tone, blood cell trafficking, permeability and immune responses. However, endothelial dysfunction results in various pathological conditions. Inflammasomes are large intracellular multimeric complexes activated by pathogens or cellular damage. Inflammasomes in vascular endothelial cells (ECs) initiate innate immune responses, which have emerged as significant mediators in endothelial dysfunction, contributing to the pathophysiology of an array of diseases. This review summarizes the mechanisms and ramifications of inflammasomes in ECs and related vascular diseases such as atherosclerosis, abdominal aortic aneurysm, stroke, and lung and kidney diseases. We also discuss potential drugs targeting EC inflammasomes and their applications in treating vascular diseases.
PubMed: 38952037
DOI: 10.1111/bph.16479 -
Journal of Clinical Neurology (Seoul,... Jul 2024Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on...
BACKGROUND AND PURPOSE
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort.
METHODS
Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene () were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population.
RESULTS
Fourteen (82%) of the 17 LSM patients had MADD with mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy.
CONCLUSIONS
Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel mutation and possibly the first ever MADD patients of Malay descent.
PubMed: 38951975
DOI: 10.3988/jcn.2023.0265