- Research Article
- 10.1016/j.ajhg.2026.03.001
Bi-allelic variants in OLA1 cause a neurodevelopmental disorder with joint hypermobility.
- Apr 01, 2026
- American journal of human genetics
- Lama Alabdi + 35 more +35
Publications from 2021 to 2026
Showing 10 of 701 papers
Bi-allelic variants in OLA1 cause a neurodevelopmental disorder with joint hypermobility.
Inter-Method Agreement of a Laboratory-Developed Qualitative CMV PCR Assay Across Multiple Non-Plasma Clinical Specimens.
This study evaluated the inter-method agreement of an in-house qualitative CMV real-time PCR assay for the detection of cytomegalovirus (CMV) DNA in various non-plasma clinical specimen types, in comparison with a commercially available comparator assay. In this prospective comparative study, 186 clinical specimens-including bronchoalveolar lavage fluid (BALF), stool, urine, colonoscopic biopsy, amniotic fluid, and intraocular fluid-were analyzed. A total of 166 samples with valid results from both test systems were included in the inter-method comparison. CMV DNA was detected using the in-house qualitative PCR assay in parallel with the comparator assay (artus® CMV QS-RGQ kit). Agreement was assessed using positive percent agreement (PPA), negative percent agreement (NPA), overall percent agreement (OPA), and Cohen's kappa coefficient (κ), in accordance with CLSI EP12-A2 recommendations. Substantial overall inter-method agreement was observed when all specimens were evaluated collectively (κ = 0.66). Agreement metrics were highest in stool, urine, and invasive specimens, whereas BALF samples demonstrated comparatively lower agreement, reflecting potential matrix-related analytical variability. The laboratory-developed qualitative CMV PCR assay demonstrated substantial inter-method agreement with the comparator assay across multiple non-plasma specimen types. The findings highlight specimen-specific variability in qualitative CMV DNA detection and represent analytical concordance between two molecular assays rather than definitive clinical diagnostic accuracy or viral load quantification.
Read moreEvaluation of the Relationship Between Adenomyosis and Cervical Elastography Parameters.
Objectives: We aim to investigate cervical biomechanical alterations associated with adenomyosis using shear-wave elastography (SWE), and to explore the discriminative potential of cervical SWE parameters. Methods: In this prospective study, 84 patients with adenomyosis, diagnosed both clinically and by ultrasonography according to the MUSA parameters, and 65 healthy women underwent elastography to the cervix with SWE. Six areas of the cervix were evaluated: anterior and posterior internal os, middle part of the cervix, and external os. Results: The adenomyosis group showed a significantly higher cervical length (27.3 ± 5.5 mm vs. 23.8 ± 4.6 mm), as well as greater anterior (11.3 ± 2.4 mm vs. 9.9 ± 1.3 mm) and posterior (11.3 ± 2.2 mm vs. 10.5 ± 1.8 mm) cervical measurements compared with the controls (p < 0.001). SWE showed higher stiffness measurements for the anterior and posterior internal os (22.3 ± 5.4 kPa and 22.2 ± 4.9 kPa) compared with the controls (15.5 ± 5.8 kPa and 15.7 ± 5.6 kPa, respectively; p < 0.001). Receiver operating characteristic analysis demonstrated high discrimination for these measurements, with area under curve values of 0.804 for the anterior internal os and 0.808 of posterior internal os. Optimal cut-offs were 17.5 kPa (sensitivity 82%, specificity 70%) and 18.5 kPa (sensitivity 81%, specificity 74%). Conclusions: Cervical elastography may serve as a non-invasive adjunctive tool for exploring disease-related biomechanical changes and for supporting imaging-based assessment of adenomyosis.
Read moreKeratin adducts in human hair prove exposure to sulfur mustard in a real case of poisoning and indicate exposure to sesquimustard and O-lost in vitro.
We herein present the development and application of a forensic mass spectrometry-based procedure simultaneously targeting hard keratins from human hair adducted with sulfur mustard (SM) and its structural analogues sesquimustard (Q) and O-lost (T). These alkylating chemicals represent blister agents banned by the Chemical Weapons Convention (CWC). The procedure was applied to an authentic hair sample of an SM-poisoned patient and thus allowed for the first time the proof of exposure to SM based on keratin adducts in a real case of poisoning. Whereas adducts of SM were detected, those of Q and T were not found. Contact of SM, Q and T with hair induced the alkylation of side chains of glutamic acid (E*) residues in diverse hard keratins (adduct formation). For analysis hair proteins were subjected to lysis to make them soluble and subsequently to proteolysis with pepsin to generate adducted peptides. Micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HR MS) allowed the detection of the three biomarker peptides AE*IRSDL, FKTIE*EL and LE*TKLQF. The characteristic alkyl-chain hydroxyethylthioethyl (HETE) was attached by SM, hydroxyethylthioethylthioethyl (HETETE) derived from Q and the hydroxyethylthioethyloxyethylthioethyl (HETEOETE)-moiety originated from exposure to T. Accordingly, we herein present an extended and improved forensic method for the biomedical verification of hair exposure to blister agents. Due to the currently growing threat by chemical warfare agents we also included some general toxicological and bioanalytical remarks of SM poisoning helpful not only for physicians and toxicologists.
Read morePrognostic Impact of Serum Albumin Levels at Diagnosis in Patients with Chronic Lymphocytic Leukemia.
Background/Objectives: Chronic lymphocytic leukemia (CLL) displays substantial clinical heterogeneity, yet access to genomic prognostic testing remains limited in many real-world and resource-constrained settings. Readily available biomarkers that reflect disease biology are therefore clinically valuable. Serum albumin, an inexpensive marker associated with systemic inflammation and tumor burden, has shown emerging prognostic potential. This study evaluated the impact of baseline albumin on time to first treatment (TTFT) and overall survival (OS) in CLL. Methods: We retrospectively analyzed adult patients with confirmed CLL treated at a single tertiary center. Baseline demographic, clinical, and laboratory features were recorded, and serum albumin was dichotomized at 4 g/dL. TTFT and OS were estimated using the Kaplan-Meier methodology. Variables with p < 0.1 in univariate analyses were included in multivariate Cox regression models. Results: A total of 230 patients were included. The median age at diagnosis was 62.5 years; 52.2% were male, and 14.8% had serum albumin <4 g/dL. Low albumin was associated with older age, advanced Rai/Binet stage, anemia, higher lymphocyte counts, and greater treatment requirement (all p < 0.05). Median follow-up was 20 months (range, 1-288). Patients with albumin <4 g/dL had inferior 5-year OS (78.4% vs. 98.7%). Although serum albumin correlated with both TTFT and OS in univariate analyses, it did not remain independently significant in multivariate models. Conclusions: While not independently prognostic, baseline serum albumin is strongly linked to adverse clinical features and poorer unadjusted survival. As a readily available, low-cost parameter, albumin may offer practical value for early risk stratification-particularly in regions where routine molecular testing is constrained.
Read moreMeier-Gorlin syndrome due to a recurrent DONSON variant in a Turkish family: first report of thumb aplasia and long-term growth data.
Meier-Gorlin syndrome (MGORS) is a rare primordial dwarfism characterized by microtia, patellar hypoplasia/aplasia, and short stature. Additional features may include skeletal, respiratory, urogenital, and endocrine abnormalities. 13 genes have been implicated, with DONSON, essential for replication fork stability and intra-S phase checkpoint activation, being the most recently identified. Only six patients with DONSON-related MGORS have been reported. This study expands the phenotype by presenting long-term follow-up and prenatal data in two affected siblings. The index patient, a 10-year-old male, had short stature, microcephaly, microtia, craniofacial features, hearing loss, patellar aplasia, and genitourinary anomalies. Despite an early growth delay, his height progressively improved without intervention. Whole-exome sequencing revealed a homozygous pathogenic c.631C>T p.(Arg211Cys) variant in DONSON (NM_017613.3). Following genetic counseling, the family declined prenatal testing in a subsequent pregnancy complicated by intrauterine growth restriction. The newborn female sibling carried the same variant and displayed DONSON-related MGORS features, including the first reported case of thumb aplasia. Additional findings in the family included renal hypoplasia, 2-4 toe syndactyly, and hypospadias. This is the third report of DONSON c.631C>T p.(Arg211Cys) in Turkish patients. While the recurrence in the same population suggests a founder effect, haplotype-based analysis is required. Thumb aplasia expands the known phenotype of DONSON-related MGORS, and the observed moderate course of growth retardation offers prognostic value. These findings highlight the importance of including DONSON in MGORS gene panels, considering population-specific variants, and systematically documenting rare phenotypic features to improve diagnosis, follow-up, and genetic counseling.
Read moreFollicular Klotho in the Ovarian Microenvironment: Exploring Its Role in IVF Outcome Prediction
Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, and key IVF success parameters. Materials and Methods: This prospective study included a total of 150 women undergoing IVF, of whom 82 had diminished ovarian reserve (DOR) and 68 had normal ovarian reserve (NOR). All participants underwent controlled ovarian stimulation using a standard antagonist protocol. During oocyte pick-up (OPU), the first aspirated follicular fluid sample was collected, processed, and analyzed for KL concentrations using a Human Klotho ELISA kit. Hormonal profiles, ovarian reserve markers, and IVF outcomes were compared between groups. Results: Follicular fluid KL levels were significantly lower in the DOR group compared with the NOR group (117.07 ± 28.88 pg/mL vs. 266.13 ± 58.29 pg/mL; p < 0.001). Anti-Müllerian hormone (AMH) levels were reduced, whereas follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were significantly higher in the DOR group (all p < 0.001). Implantation and clinical pregnancy rates were also significantly lower in the DOR group compared with the NOR group (p < 0.001 and p = 0.003, respectively). KL levels showed a strong positive correlation with the number of fertilized oocytes in both groups (DOR: r = 0.690; NOR: r = 0.552). Each one-unit increase in KL was associated with a 3.7% increase in implantation probability and a 3.2% increase in clinical pregnancy probability in the DOR group, and with corresponding increases of 4.4% and 1.2% in the NOR group (all p < 0.05). Conclusions: This study demonstrates significant associations between follicular fluid KL levels and fertilization, implantation, and clinical pregnancy outcomes. These associations appear to be more pronounced than those observed with traditional ovarian reserve markers such as AMH and antral follicle count. Reduced KL levels are associated with fewer fertilized oocytes, whereas higher KL concentrations correspond to increased implantation and clinical pregnancy probabilities. Nevertheless, similar to other non-invasive biomarkers, current evidence is insufficient to support routine clinical use of KL. Large-scale, well-designed, multicenter studies are therefore required to validate its clinical relevance and to determine whether KL can serve as a reliable and practical predictor of IVF success.
Read moreAssessing physicians' experiences with a clinical decision support system in patient blood management programme: a cross-sectional observational study.
2865P Association of skeletal muscle and visceral FDG uptake with cancer cachexia, nutritional status, and survival in small cell lung cancer
PATERNALİST LİDERLİK MODELİNİN İNSAN KAYNAKLARI YÖNETİMİ ÜZERİNDEKİ ETKİSİ
Farklı kültür ve toplum yapılarında yöneticilerden beklenen liderlik tarzlarının da değişkenlik gösterdiği görülmektedir. Bu doğrultuda çalışmanın amacı, öncelikle liderlik modellerine genel bir bakış sunmak, ardından paternalist liderlik kavramını açıklamak ve nihayetinde paternalist liderlik yaklaşımı ile insan kaynakları yönetimi arasındaki ilişkiyi incelemektir. Nitel araştırma yöntemlerinden doküman incelemesi yoluyla veriler toplanmış olup literatüre dökülmüştür. Araştırma sonuçlarına bakıldığında paternalist liderliğin insan kaynakları çalışanlarının performanslarına olumlu katkıda bulunduğu gözlenmiştir. Özellikle iş birliğine dayalı yapıların ve yüksek güç mesafesinin hâkim olduğu Doğu toplumlarında paternalist liderlik anlayışının daha yaygın olduğu dikkat çekmektedir. Paternalizm, örgütsel hiyerarşi içerisinde liderin kuruluşu bir aile yapısına benzeterek astlarının hem kişisel hem de mesleki hayatlarında rehberlik ettiği ve destek sağladığı, buna karşılık astlardan kendisine ve örgüte karşı sadakat ile bağlılık beklediği bir yaklaşımı ifade etmektedir.
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