Publications by authors named "Sandra von Hardenberg"
Allergol Select
October 2024
Article Synopsis
- Primary atopic disorders (PAD) are rare genetic conditions caused by specific gene variants that affect skin and immune function, making diagnosis challenging among common allergic disease cases.
- Identifying PAD requires recognizing clinical red flags like family history and unusual infections, as conventional lab tests are inadequate for definitive diagnosis.
- Whole-genome sequencing (WGS) enhances diagnostic efficiency and accuracy, but requires careful interpretation and collaboration among specialists to effectively manage PAD cases.
Br J Haematol
December 2024
Article Synopsis
- - Shwachman-Diamond syndrome is a complex disorder that involves both genetic and clinical variation, and this report focuses on a particularly severe case in an infant.
- - The infant was found to have two specific EFL1 gene mutations (c.89A>G and c.2599A>G) that were inherited from each parent, contributing to the severity of the syndrome.
- - Laboratory analyses of cells from the patient indicated that these mutations disrupted the production of functional ribosomes, which hindered protein synthesis and led to the critical health issues observed in this case.
Front Immunol
September 2024
Article Synopsis
- STAT3 gain-of-function syndrome is an immune disorder that results in various immune system issues, often requiring immunomodulatory treatments like blocking interleukin-6 receptors or using JAK inhibitors (JAKi).
- A study at Hannover University involved seven patients with STAT3-GOF, where five were treated with JAK inhibitors, leading to positive outcomes for many autoimmune and inflammatory symptoms.
- Overall, JAKi treatment showed significant improvement for the majority of patients, but more long-term studies are necessary to understand the risks associated with extended use.
Article Synopsis
- Primary ciliary dyskinesia (PCD) is a rare genetic disorder that affects ciliary function, leading to airway clearance issues and sometimes organ positioning defects (laterality defects), with a study conducted across 19 countries to analyze gene defects and their clinical implications.
- The study involved 1236 individuals with a variety of pathogenic DNA variants and found significant geographical differences in PCD genotypes, with varying rates of laterality defects and distinct genetic characteristics linked to different countries.
- Results revealed that individuals with PCD often have lower lung function (measured by forced expiratory volume) and that the presence of certain genetic variants can correlate with more severe clinical outcomes, highlighting the importance of genetic understanding in diagnosing
J Allergy Clin Immunol
October 2024
Article Synopsis
- Human tapasin deficiency leads to a significant reduction in MHC-I expression on the cell surface, which is linked to immune system issues and increased susceptibility to infections like herpes zoster.
- A novel genetic variant in the TAPBP gene was found in a patient, resulting in this deficiency, and laboratory tests showed the deficiency affects both the transport proteins (TAP1 and TAP2) and MHC-I trafficking to the membrane.
- Treatment with IFN-α was shown to enhance MHC-I expression on the surface of affected cells, providing a possible therapeutic direction for those with tapasin deficiency.
Article Synopsis
- * Rapid genomic sequencing has proven to be highly valuable in diagnosing these conditions, showing that quicker molecular diagnoses can positively impact clinical management.
- * Early identification through genomic sequencing can facilitate precision medicine treatments, improve patient outcomes, and potentially lead to reduced healthcare costs.
Article Synopsis
- New technologies in genetic diagnostics have greatly enhanced the understanding and management of rare diseases, particularly inborn errors of immunity (IEI), which compromise the immune system and lead to various health issues.
- Advanced diagnostic techniques like gene sequencing and proteomics help identify genetic causes of IEI and offer insights into their underlying mechanisms.
- The integration of genetic testing in clinical practice allows for early diagnosis and personalized treatment, but challenges such as variant interpretation and handling vast amounts of genetic data persist.
Article Synopsis
- SNURPORTIN-1 (SNUPN) is important for transporting proteins in the cell but its exact job wasn’t known before.
- Researchers studied 18 kids with a rare type of muscular dystrophy and found that changes in the SNUPN gene might be causing their health issues.
- The study showed that the faulty SNUPN protein doesn't work properly, leading to problems in muscle cells and causing symptoms of muscular dystrophy in these kids.
Article Synopsis
- Researchers identified a genetic cause for a rare neurodevelopmental syndrome characterized by cognitive impairment, distinctive facial features, and various additional health issues.
- They studied six individuals from unrelated families using exome sequencing and created models with human stem cells and zebrafish to examine the effects of the identified gene, CACHD1.
- Results showed that mutations in CACHD1 lead to significant neural development problems and physical defects, linking it directly to the syndrome’s symptoms.
Am J Pathol
February 2024
Article Synopsis
- * Researchers compared lung tissue samples from children with ACD, adults with non-specific interstitial pneumonia, and healthy controls, using advanced techniques like transmission electron microscopy and transcriptome profiling.
- * Findings revealed that in ACD, capillary basement membranes are abnormally thick and multilayered, while certain gene expressions related to vascular structure are altered, suggesting potential therapeutic targets to address these abnormalities.
Article Synopsis
- - Whole-exome sequencing helps diagnose primary ciliary dyskinesia (PCD) but often uncovers variants of uncertain significance (VUS), complicating results in about 30% of patients.
- - The study focused on 16 adults with bronchiectasis and inconclusive whole-exome sequencing results, using transmission electron microscopy (TEM) and specialized software to analyze ciliary structures.
- - Results showed that while eight patients had normal ciliary structure, six exhibited notable defects linked to VUS, and one had a defect confirming clinical relevance, indicating that TEM can effectively clarify genotype-phenotype correlations in PCD cases.
Pediatr Pulmonol
November 2023
Article Synopsis
- Fibroblast growth factor 10 (FGF10) is crucial for lung development and can lead to serious conditions like LADD syndrome when mutated.
- This study examines four children with complications from childhood Interstitial Lung Disease (chILD) linked to heterozygous FGF10 mutations, highlighting their severe respiratory issues.
- Findings indicate that even without notable syndromic features, FGF10-related disorders should be considered in children facing postnatal respiratory distress, as they may lead to severe outcomes, including pulmonary hypertension and lung fibrosis.
Article Synopsis
- Rare genetic diseases significantly affect children's health, and whole exome sequencing (WES) is an effective method for diagnosing these conditions, especially when complemented by parental sequencing (trio WES).
- In a study of 224 pediatric patients, trio WES yielded a diagnosis in 30% of cases and significantly decreased the analysis turnaround time from 41 days to 23 days between 2019 and 2021, with some new genetic syndromes identified.
- The findings highlight the importance of incorporating trio WES with copy number variant analysis in early diagnostics for children, particularly in ICU settings, to improve the likelihood of timely and accurate diagnoses of suspected monogenic diseases.
Article Synopsis
- - Monogenic autoinflammatory diseases (AID) are genetic conditions that lead to unexplained or excessive inflammation due to defects in the innate immune system, and accurate diagnosis relies on identifying specific genetic variants.
- - Researchers conducted whole exome sequencing (WES) on 125 children suspected of having monogenic AID, using a step-wise strategy that first analyzed a small panel of known relevant genes, then expanded to a larger gene panel.
- - The study found that analyzing the smaller gene panel (13 genes) diagnosed 16% of patients, while the larger panel (542 genes) diagnosed 20.8%, but WES analysis did not improve diagnostic yield, indicating that targeted gene panels are sufficient for early diagnosis in
Am J Med Genet A
May 2023
Article Synopsis
- AMOTL1 is a gene that codes for a protein involved in regulating cell behavior, including how cells stick together and move.
- A study identified specific mutations in AMOTL1 that are linked to a set of health issues, including orofacial clefting, congenital heart disease, tall stature, ear abnormalities, and gastrointestinal problems.
- The findings suggest that certain variants in AMOTL1, particularly those affecting a critical region of the protein, are associated with a new syndrome characterized by these conditions.
Front Immunol
October 2022
Article Synopsis
- Gain-of-function variants in the STING gene are responsible for STING-Associated Vasculopathy with onset in Infancy (SAVI), previously thought to only occur with heterozygous mutations.
- Recent findings highlight a specific homozygous variant, c.841C>T, causing SAVI in four unrelated patients, all presenting with interstitial lung disease and varying disease severity.
- This research challenges the established view of SAVI as an autosomal dominant condition, suggesting an autosomal recessive inheritance pattern and potentially aiding in diagnosis and treatment approaches.
Int Arch Allergy Immunol
January 2023
Article Synopsis
- Next-generation sequencing (NGS) has a limited success rate (under 30%) in diagnosing monogenic inborn errors of immunity (IEI), particularly for conditions linked to CTLA-4 gene mutations.
- The study focused on identifying genetic causes of familial immunodeficiency when conventional single nucleotide variant analysis of NGS did not provide results, utilizing analysis of copy number variants (CNVs).
- A novel mutation in CTLA-4 was discovered, highlighting the importance of CNV analysis to improve diagnostic outcomes in immunodeficiency cases.
PLoS Comput Biol
September 2022
Article Synopsis
- Next-generation sequencing (NGS) allows for the cost-effective sequencing of large gene panels, but interpreting the resultant sequence variants is complex, error-prone, and inconsistent across labs.
- To address these challenges, the ACMG/AMP have established guidelines for variant interpretation, particularly beneficial for analyzing disorders with many associated genes, like hearing impairment.
- The GenOtoScope tool was developed to automate this variant analysis, demonstrating superior accuracy and precision compared to other tools, thus streamlining the classification process for genetic variants linked to hearing loss.
Article Synopsis
- * Of the 219 patients studied, 12.3% were diagnosed with cancer, with gastric cancer, non-melanoma skin cancer, and non-Hodgkin lymphoma being the most common types. Certain immune-related health issues were found to be linked to cancer diagnoses.
- * Genetic testing identified potential inherited cancer risks in about 14.3% of these patients, suggesting that some CVID patients may have a genetic predisposition to certain cancers.
Klin Padiatr
September 2022
Article Synopsis
- Pulmonary Alveolar Microlithiasis (PAM) is a rare hereditary lung disease caused by mutations in the solute family 34 member 2 gene, leading to calcium phosphate crystal buildup in the lungs.
- More than 1000 cases have been reported, with symptoms often ranging from asymptomatic to slow progression towards respiratory failure in middle age.
- Treatment for PAM is limited, and lung transplantation is the only viable option for patients with advanced disease; the article also presents a new case involving an adolescent migrant from East Africa.
J Clin Immunol
February 2022
Article Synopsis
- DNA damage is a common occurrence in cells caused by factors like radiation and certain drugs, and the DNA damage response (DDR) system works to repair this damage, prevent tumors, and maintain cell health.
- This study evaluated specific DDR biomarkers (γH2AX, p-ATM, and p-CHK2) in patients with immunodeficiencies due to defects in DNA repair mechanisms, finding reduced responses in patients with ataxia telangiectasia and unusual delayed responses in those with non-homologous end-joining defects.
- While these biomarkers can help diagnose certain types of DNA repair issues, they have limitations and may not reliably identify all deficiencies, such as ARTEMIS deficiency, highlighting the need for careful
Article Synopsis
- * The study investigates how changes in microRNAs (miRNAs) in endothelial progenitor cells (EPC) are connected to preeclampsia, revealing distinct miRNA levels in both maternal and cord blood EPCs between preeclamptic and healthy samples.
- * Specifically, the miRNA hsa-miR-1270 showed notable differences and was linked to reduced cellular functions in EPCs, suggesting that understanding these epigenetic changes could lead to targeted therapies for preeclampsia-related complications.
J Allergy Clin Immunol
August 2021
Article Synopsis
- The study focuses on a specific genetic deficiency related to ZNFX1, which is crucial for regulating antiviral immune responses to viral nucleic acids.
- Researchers examined 15 patients from 8 families who showed severe reactions to both RNA and DNA viral infections, including chronic inflammation and organ issues.
- The findings revealed harmful genetic variants in ZNFX1 among patients, leading to unbalanced interferon-stimulated gene expression and difficulties in clearing viral infections.
