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DNA and Cell Biology May 2024Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain...
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of but also enhances our understanding of the mechanisms connecting with overgrowth syndromes.
PubMed: 38700464
DOI: 10.1089/dna.2023.0391 -
The Journal of the Association of... Sep 2023The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress,... (Review)
Review
The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.
Topics: Humans; Anti-Bacterial Agents; Dysbiosis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Irritable Bowel Syndrome; Prebiotics; Probiotics
PubMed: 38700306
DOI: 10.59556/japi.71.0353 -
BMC Medical Genomics Apr 2024Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and...
OBJECTIVE
Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses.
DESIGN&METHODS
A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted.
RESULTS
All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant.
CONCLUSION
This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.
Topics: Humans; Histone-Lysine N-Methyltransferase; Sotos Syndrome; Male; Female; Child, Preschool; Child; Infant; Intracellular Signaling Peptides and Proteins; Exome Sequencing; Mutation; Karyotyping; Histone Methyltransferases; Nuclear Proteins
PubMed: 38684994
DOI: 10.1186/s12920-024-01889-5 -
Journal of Clinical Medicine Apr 2024Sotos syndrome is a genetic disorder caused by gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly,... (Review)
Review
Sotos syndrome is a genetic disorder caused by gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly, learning disabilities, and co-occurring neuropsychiatric symptoms. Literature sources published in 2002-2023 were selected and analyzed from PubMed and Google Scholar databases. Neuropsychiatric symptoms are observed among children and adolescents with Sotos syndrome. The majority have intellectual disabilities or borderline intellect. Verbal IQ is higher than performance IQ. Individuals display difficulties in expressing language. Aggression is reported by parents. Children express autistic behavior, ADHD, anxiety based on phobias, and early bedtime-wake times. Sotos syndrome is associated with neuropsychiatric disorders in children. Slow intellectual and language development, aggressive outbursts, anxiety, autism spectrum disorder, and hyperactivity are present in the newest studies. Comprehensive assistance is needed for Sotos syndrome patients in responding to areas of difficulty. There is still a lack of research on the developmental characteristics of these children and the possibilities of improving psychosocial adaptation by providing multidisciplinary long-term medical, educational, and social care.
PubMed: 38673476
DOI: 10.3390/jcm13082204 -
Nutrition (Burbank, Los Angeles County,... Aug 2024The prevalence of small intestinal bacterial overgrowth (SIBO) is rising worldwide, particularly in nations with high rates of urbanization. Irritable bowel syndrome,... (Review)
Review
The prevalence of small intestinal bacterial overgrowth (SIBO) is rising worldwide, particularly in nations with high rates of urbanization. Irritable bowel syndrome, inflammatory bowel illnesses, and nonspecific dysmotility are strongly linked to SIBO. Moreover, repeated antibiotic therapy promotes microorganisms' overgrowth through the development of antibiotic resistance. The primary cause of excessive fermentation in the small intestine is a malfunctioning gastrointestinal motor complex, which results in the gut's longer retention of food residues. There are anatomical and physiological factors affecting the functioning of the myoelectric motor complex. Except for them, diet conditions the activity of gastrointestinal transit. Indisputably, the Western type of nutrition is unfavorable. Some food components have greater importance in the functioning of the gastrointestinal motor complex than others. Tryptophan, an essential amino acid and precursor of the serotonin hormone, accelerates intestinal transit, and gastric emptying, similarly to fiber and polyphenols. Additionally, the effect of food on the microbiome is important, and diet should prevent bacterial overgrowth and exhibit antimicrobial effects against pathogens. Therefore, knowledge about proper nutrition is essential to prevent the development and recurrence of SIBO. Since the scientific world was unsure whether there was a long-term or potential solution for SIBO until quite recently, research on a number of the topics included in the article should be performed. The article aimed to summarize current knowledge about proper nutrition after SIBO eradication and the prevention of recurrent bacterial overgrowth. Moreover, a connection was found between diet, gut dysmotility, and SIBO.
Topics: Humans; Gastrointestinal Motility; Gastrointestinal Microbiome; Diet; Blind Loop Syndrome; Intestine, Small; Food
PubMed: 38657418
DOI: 10.1016/j.nut.2024.112464 -
Neurogastroenterology and Motility Jul 2024Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test,...
BACKGROUND
Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE.
METHODS
In 75 patients with DGE and dyspepsia, we tested for SIBO (≥10 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO.
KEY RESULTS
Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006).
CONCLUSIONS & INFERENCES
Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.
Topics: Humans; Female; Male; Middle Aged; Intestine, Small; Adult; Aged; Gastric Emptying; Gastrointestinal Diseases; Blind Loop Syndrome; Diabetes Complications; Breath Tests; Risk Factors
PubMed: 38651669
DOI: 10.1111/nmo.14798 -
Diabetes, Metabolic Syndrome and... 2024Pituitary stalk interruption syndrome is a relatively rare disease. Patients with this disease usually have different degrees of short stature in adulthood. The purpose...
Pituitary Stalk Interruption Syndrome with Excessive Height Growth Combined with Congenital Absence of the Uterus and Ovaries: A Rare Case Report and Review of the Literature.
AIM
Pituitary stalk interruption syndrome is a relatively rare disease. Patients with this disease usually have different degrees of short stature in adulthood. The purpose of this case report is to highlight a special case of unusually elongated limbs with excessive height growth and congenital absence of uterus and ovary, so as to improve clinicians understanding of the atypical manifestations of pituitary stalk interruption syndrome and provide reference for the clinical diagnosis and treatment of the disease.
CASE PRESENTATION
The 30-year-old female patient exhibited disproportionate growth in height, with a significant increase from 140 cm at the age of 16 to 180 cm currently. Physical examination revealed widened bilateral eye fissures, underdeveloped secondary sexual characteristics, and absence of menstruation. The patient 's parents are cousins, belonging to consanguineous marriage. The patient 's hypoglycemia provocation test suggested the lack of growth hormone and cortisol. Gonadorelin provocation test suggested hypogonadism, and thyroid function test showed hypothyroidism. Pituitary MRI plain scan and enhancement suggested pituitary stalk interruption syndrome, and abdominal and urinary color Doppler ultrasound suggested no echo of uterus and bilateral appendages in the pelvic cavity. The karyotype of peripheral blood was 45, X[3] / 46, XX [117]. The patient was diagnosed with pituitary stalk interruption syndrome, congenital uterine and ovarian deficiency, bone overgrowth, hypothyroidism and secondary osteoporosis. During hospitalization, the symptoms were improved and discharged after hormone replacement therapy such as physiological dose of glucocorticoid, estradiol valerate tablets and levothyroxine sodium tablets. Now the patient is still in our hospital endocrinology outpatient follow-up, no special discomfort.
CONCLUSION
The patient had special clinical manifestations and was clinically confirmed as pituitary stalk interruption syndrome. The patient 's height continues to grow in the absence of growth hormone in the body, and its mechanism remains to be further studied.
PubMed: 38645656
DOI: 10.2147/DMSO.S456678 -
BMJ Case Reports Apr 2024Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals...
Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals aged 20-40 years but is rarely seen in children. We report a case of an infant with Rubenstein-Taybi syndrome presenting with nebulo-macular corneal opacity and congenital pterygium. On examination under anaesthesia, bilateral infero-nasal nebulo-macular corneal opacity (6 × 5 mm) with a whitish pink tissue originating from nasal bulbar conjunctiva was noticed. The probe test was negative for this tissue. To the best of our knowledge, only two other cases of congenital pterygium have been reported in the literature. The presence of this anomaly supports the hypothesis of genetic factors having a role in the development of pterygium.
Topics: Infant; Child; Humans; Pterygium; Rubinstein-Taybi Syndrome; Cornea; Corneal Opacity; Conjunctiva; Eye Abnormalities
PubMed: 38642933
DOI: 10.1136/bcr-2023-257962 -
Gut Microbes 2024To determine the efficacy of the probiotic CECT 7347 (ES1) and postbiotic heat-treated CECT 7347 (HT-ES1) in improving symptom severity in adults with... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live CECT 7347 (ES1) and heat-treated CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome.
To determine the efficacy of the probiotic CECT 7347 (ES1) and postbiotic heat-treated CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) ( < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) ( < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.
Topics: Adult; Humans; Irritable Bowel Syndrome; Quality of Life; Hot Temperature; Gastrointestinal Microbiome; Bifidobacterium longum; Diarrhea; Peptides, Cyclic
PubMed: 38630015
DOI: 10.1080/19490976.2024.2338322