ESMO Open. 2024 Apr;9(4):102981. doi: 10.1016/j.esmoop.2024.102981. Epub 2024 Apr 12.

ABSTRACT

BACKGROUND: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP.

MATERIALS AND METHODS: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response.

RESULTS: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively).

CONCLUSION: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.

PMID:38613908 | PMC:PMC11033064 | DOI:10.1016/j.esmoop.2024.102981

BMC Anesthesiol. 2024 Apr 13;24(1):143. doi: 10.1186/s12871-024-02508-7.

ABSTRACT

BACKGROUND: The Koolen-de Vries syndrome (KdVS) is a relatively new rare disease caused by micro-deletion of 17q21.31 which was first reported by Koolen in 2006. Typical phenotypes for KdVS include hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Up to now, there was only one case report about anesthesia management of patient diagnosed KdVS. It was a 2-year-old girl who experienced an MRI exam under anesthesia.

CASE PRESENTATION: We described a 21-month-old boy who planned to undergo an orchidopexy under general anesthesia diagnosed with KdVS. He had an intellectual disability, characteristic facial dysmorphism, tracheo/laryngomalacia, patent foramen ovale, and cryptorchidism related to KdVS. Due to the complex condition especially the presence of tracheo/laryngomalacia, we took some special measures, including reducing the amount of long-acting opioid, keeping the spontaneous breath, performing a caudal block, and applying the laryngeal mask. But the laryngeal mask was changed to an endotracheal tube because it failed to provide adequate ventilation. The boy experienced mild laryngeal spasm and hypoxia after extubation, but lateral position and etomidate eased his breathing problem and re-intubation was avoided. It is indicated that anesthesia management for patients with orphan disease is a real challenge for all anesthesia providers.

CONCLUSIONS: The Koolen-de Vries syndrome is a relatively new orphan disease involving multiple systems. Keeping spontaneous breath, evaluating airway potency to anesthetics, applying endotracheal tube, and post-extubation lateral or prone position may be helpful for airway management for patient with hypotonia and tracheo/laryngomalacia. KdVS patient needs prolonged post-anesthesia monitoring and/or medication for airway complications.

PMID:38614993 | DOI:10.1186/s12871-024-02508-7

J R Coll Physicians Edinb. 2024 Mar;54(1):41-43. doi: 10.1177/14782715241237283.

ABSTRACT

Whipple's disease is a multisystemic chronic infectious condition caused by Tropheryma whipplei (T. whipplei). Though characterised often by insidious weight loss, diarrhoea, and arthralgia, three other distinct manifestations can be observed, namely localised disease, acute infection and asymptomatic carriage. The diagnosis relies on histopathological examination of duodenal biopsies and polymerase chain reaction analysis of the 16S rRNA gene for T. whipplei. We report the case of a middle-aged man admitted for etiologic investigation of prolonged, migrating, and inflammatory arthralgias and subsequent development of gastrointestinal symptoms. Despite its reputation as a great mimicker of many different illnesses, the difficulty in diagnosis probably lies with its rarity rather than its masking.

PMID:38606805 | DOI:10.1177/14782715241237283

Pathol Oncol Res. 2024 Mar 28;30:1611705. doi: 10.3389/pore.2024.1611705. eCollection 2024.

ABSTRACT

BACKGROUND: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder.

CASE PRESENTATION: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment.

CONCLUSION: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.

PMID:38605931 | PMC:PMC11007090 | DOI:10.3389/pore.2024.1611705

Eur J Paediatr Neurol. 2024 Mar;49:A1. doi: 10.1016/j.ejpn.2024.04.002. Epub 2024 Apr 6.

NO ABSTRACT

PMID:38600015 | DOI:10.1016/j.ejpn.2024.04.002

J Neurol Sci. 2024 May 15;460:122989. doi: 10.1016/j.jns.2024.122989. Epub 2024 Apr 3.

ABSTRACT

Rare diseases are characterized by substantial unmet need mostly because the majority have limited, or no treatment options and a large number also affect children. Since the inception of EU orphan regulation in 2000 the European Medicines Agency Committee for Orphan Medicinal Products has received several applications for paediatric rare neuromuscular diseases (PERAN) however treatment options remain limited. Here we discuss the results form an observational, retrospective, cross-sectional study to characterize the currently authorised orphan medicinal products (OMP) and orphan designations (OD) given to products for PERAN in the last two decades. In the EU about half of PERAN diseases have at least one active OD approved since 2000, and about half of these are for Duchenne muscular dystrophy (DMD). The large majority of PERAN diseases do not have an authorised medicine with only 6 OMP currently authorised for Spinal muscular atrophy (3); DMD (1) and Myasthenia gravis (2). One in five products have inactive or discontinued regulatory development but clinical trials are ongoing for the vast majority of PERAN diseases, and more than half are in the final stage of clinical research with significantly more products with medical plausibility based in clinical data reaching advanced stages in clinical development.

PMID:38581740 | DOI:10.1016/j.jns.2024.122989

Orphanet J Rare Dis. 2024 Apr 6;19(1):147. doi: 10.1186/s13023-024-03162-5.

ABSTRACT

BACKGROUND: Patient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem.

METHODS: In the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted.

RESULTS: In total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and "other" geographical scope were ranked at the bottom of the list with the lowest proportion. Responders' willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed.

CONCLUSIONS: The most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data.

PMID:38582900 | DOI:10.1186/s13023-024-03162-5

Transfus Med Rev. 2024 Apr;38(2):150825. doi: 10.1016/j.tmrv.2024.150825. Epub 2024 Mar 15.

NO ABSTRACT

PMID:38579548 | DOI:10.1016/j.tmrv.2024.150825

Immunol Allergy Clin North Am. 2024 May;44(2):293-298. doi: 10.1016/j.iac.2024.01.002. Epub 2024 Feb 19.

ABSTRACT

Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine.

PMID:38575224 | DOI:10.1016/j.iac.2024.01.002

Rev Med Suisse. 2024 Apr 3;20(868):699-704. doi: 10.53738/REVMED.2024.20.868.699.

ABSTRACT

Mixed connective tissue disease (MCTD) is a rare autoimmune condition. Since its first description 50 years ago, its mere existence has been debated, given that it shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis and Sjogren's syndrome. Also, while antibodies to U1-RNP are essential for the diagnosis of MCTD, these antibodies may be expressed in other circumstances, such as in case of SLE. Nevertheless, the patient fulfilling criteria for MCTD needs specific management. In this review, we describe the clinical features and the potential complications of this complex disease, often wrongly disregarded as benign. We will also emphasize the recommended follow-up exams and address treatment, which is currently lacking formal recommendations.

PMID:38568063 | DOI:10.53738/REVMED.2024.20.868.699

Am J Hum Genet. 2024 Mar 27:S0002-9297(24)00081-8. doi: 10.1016/j.ajhg.2024.03.008. Online ahead of print.

ABSTRACT

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

PMID:38565148 | DOI:10.1016/j.ajhg.2024.03.008

Pharmacoepidemiol Drug Saf. 2024 Apr;33(4):e5778. doi: 10.1002/pds.5778.

ABSTRACT

PURPOSE: In rare diseases, real-world evidence (RWE) generation is often restricted due to small patient numbers and global geographic distribution. A federated data network (FDN) approach brings together multiple data sources harmonized for collaboration to increase the power of observational research. In this paper, we review how to increase reproducibility and transparency of RWE studies in rare diseases through disease-specific FDNs.

METHOD: To be successful, a multiple stakeholder scientific FDN collaboration requires a strong governance model in place. In such a model, each database owner remains in full control regarding the use of and access to patient-level data and is responsible for data privacy, ethical, and legal compliance. Provided that all this is well documented and good database descriptions are in place, such a governance model results in increased transparency, while reproducibility is achieved through data curation and harmonization, and distributed analytical methods.

RESULTS: Leveraging the OHDSI community set of methods and tools, two rare disease-specific FDNs are discussed in more detail. For multiple myeloma, HONEUR-the Haematology Outcomes Network in Europe-has built a strong community among the data partners dedicated to scientific exchange and research. To advance scientific knowledge in pulmonary hypertension (PH) an FDN, called PHederation, was established to form a partnership of research institutions with PH databases coming from diverse origins.

PMID:38556812 | DOI:10.1002/pds.5778

Mol Genet Metab. 2024 May;142(1):108444. doi: 10.1016/j.ymgme.2024.108444. Epub 2024 Mar 14.

ABSTRACT

Alpha-mannosidosis is an ultra-rare lysosomal disease that is caused by variants of the MAN2B1 gene on chromosome 19p13. These variants result in faulty or absent alpha-mannosidase in lysosomes, which leads to intracellular accumulation of mannose-containing oligosaccharides. Diagnosis of alpha-mannosidosis is often delayed, in part because of the rarity of the disease, its gradual onset and heterogeneity of presentation, but also because of the similarity of many signs and symptoms of the disease to those of other lysosomal diseases. Treatment of alpha-mannosidosis was previously limited to hematopoietic stem cell transplantation, but outcomes are variable and not all patients are eligible or have a suitable donor. Recently, an enzyme replacement therapy, recombinant human alpha-mannosidase (velmanase alfa), was approved for the treatment of non-neurological manifestations in adult and pediatric patients with alpha-mannosidosis. Treatment with velmanase alfa reduces serum levels of oligosaccharides, increases levels of immunoglobulin G, and improves patients' functional capacity and quality of life, although it is not effective for the neurologic phenotype because it does not cross the blood-brain barrier. Since the effects of velmanase alfa are more marked in children than adults, early diagnosis to allow early initiation of treatment has become more important. To support this, patient, parent/caregiver, and clinician awareness and education is imperative. A number of approaches can be taken to meet this goal, such as the development of disease registries, validated diagnostic algorithms, and screening tools, improved under-/post-graduate clinician education, easily accessible and reliable information for patients/families (such as that made available on the internet), and the formation of patient advocacy groups. Such approaches may raise awareness of alpha-mannosidosis, reduce the diagnostic delay and thus improve the lives of those affected.

PMID:38555683 | DOI:10.1016/j.ymgme.2024.108444

J Endocrinol Invest. 2024 Apr 1. doi: 10.1007/s40618-024-02365-8. Online ahead of print.

ABSTRACT

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients.

METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin).

RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN.

CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

PMID:38556572 | DOI:10.1007/s40618-024-02365-8

Front Endocrinol (Lausanne). 2024 Mar 13;15:1345067. doi: 10.3389/fendo.2024.1345067. eCollection 2024.

ABSTRACT

BACKGROUND: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported.

METHODS: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date.

RESULTS: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades.

CONCLUSION: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

PMID:38544690 | PMC:PMC10965776 | DOI:10.3389/fendo.2024.1345067

Genes (Basel). 2024 Mar 17;15(3):370. doi: 10.3390/genes15030370.

ABSTRACT

Genomic variant prioritization is crucial for identifying disease-associated genetic variations. Integrating facial and clinical feature analyses into this process enhances performance. This study demonstrates the integration of facial analysis (GestaltMatcher) and Human Phenotype Ontology analysis (CADA) within VarFish, an open-source variant analysis framework. Challenges related to non-open-source components were addressed by providing an open-source version of GestaltMatcher, facilitating on-premise facial analysis to address data privacy concerns. Performance evaluation on 163 patients recruited from a German multi-center study of rare diseases showed PEDIA's superior accuracy in variant prioritization compared to individual scores. This study highlights the importance of further benchmarking and future integration of advanced facial analysis approaches aligned with ACMG guidelines to enhance variant classification.

PMID:38540429 | DOI:10.3390/genes15030370

Biomolecules. 2024 Mar 14;14(3):349. doi: 10.3390/biom14030349.

ABSTRACT

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

PMID:38540768 | DOI:10.3390/biom14030349

S Afr Med J. 2023 Dec 4;113(12):9. doi: 10.7196/SAMJ.2023.v113i12.1507.

NO ABSTRACT

PMID:38525623 | DOI:10.7196/SAMJ.2023.v113i12.1507

Reumatismo. 2024 Mar 22;76(1). doi: 10.4081/reumatismo.2024.1621.

ABSTRACT

OBJECTIVE: Melorheostosis is a rare, non-hereditary, benign bone disease characterized by abnormal bone growth. Generally, melorheostosis develops during childhood or adolescence and progresses gradually over time. This disease represents a true challenge to the physician because of its variability due to location, extension of the affected bone, and involvement of associated soft tissue. Pain management, physical therapy, and surgery may be recommended, depending on the individual case. This review aims to get an overview of the latest evidence relating to epidemiology, clinical and radiographic characteristics, diagnosis, and possible therapeutic strategies for melorheostosis and describe our experience through a clinical case.

METHODS: We designed a comprehensive literature search on melorheostosis in MEDLINE (via Pubmed) up to April 2023 and reviewed reports published in international journals.

RESULTS: The purpose is to highlight the importance of a multidisciplinary approach in the management of a rare disease such as melorheostosis. We discuss the role of different physicians, including genetists, rheumatologists, physiatrists, physical therapists, and orthopedic surgeons, in providing accurate diagnoses and effective treatments. We conducted a comprehensive review of the literature on the treatment of melorheostosis to support these findings. In addition, the article presents a case study of a patient suffering from melorheostosis, focusing on difficulties in reaching a correct diagnosis and attempts towards conservative and surgical interventions. The patient underwent hip arthroplasty, and the final result was an improvement in function and a reduction in pain.

CONCLUSIONS: Managing melorheostosis can be challenging, and there is no standardized treatment for this condition at the moment.

PMID:38523583 | DOI:10.4081/reumatismo.2024.1621

Birth Defects Res. 2024 Mar;116(3):e2331. doi: 10.1002/bdr2.2331.

ABSTRACT

BACKGROUND: Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism.

METHODS: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios.

RESULTS: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10-7), rs45580033 (ASB2, p = 4.2 × 10-10), and rs75426652 (LHPP, p = 7.2 × 10-14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants.

CONCLUSIONS: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.

PMID:38526198 | DOI:10.1002/bdr2.2331