Preimplantation genetic testing for Neurofibromatosis type 1: more than 20 years of clinical experience

Vernimmen, Vivian; Paulussen, Aimée D. C.; Dreesen, Jos C. F. M.; van Golde, Ron J.; Zamani Esteki, Masoud; Coonen, Edith; van Buul-van Zwet, Marianne L.; Homminga, Irene; Derijck, Alwin A. H. A.; Brandts, Lloyd; Stumpel, Constance T. R. M.; de Die-Smulders, Christine E. M.

doi:10.1038/s41431-023-01404-x

Cited by 7 publications

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the UK and US consensus management guidelines (Ferner et al, 2007;Stewart et al, 2018). Genetic testing is used in exceptional cases, especially in prenatal or preimplantation diagnosis (Vernimmen et al, 2023). These tests are prohibitively expensive, yet a positive NF1 mutation test does not predict the severity or complications of the disorder (Tamura, 2021).…”

Section: Discussionsupporting

confidence: 80%

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya

Onyango,

Mutuma,

Gachie

et al. 2024

Am. J. Med. Sci. Innov.

View full text Add to dashboard Cite

Neurofibromatosis 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene, with near complete penetrance and variable clinical presentation. Patients classically have café-au-lait macules, neurofibromas, skin freckles, and Lisch nodules, among other multisystemic features. Long-term management in a multidisciplinary team focuses on surveillance and treating complications. NF1 is a rare disease in Kenya, often leading to myths and misconceptions about its nature, especially among rural communities. We present a classical case from rural Kenya whose diagnosis was delayed by a belief that it was the result of a curse. We aim to highlight the importance of making this diagnosis and its linkage to a long-term care plan within a primary health care setting.

show abstract

Section: Discussionsupporting

confidence: 80%

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya

Onyango,

Mutuma,

Gachie

et al. 2024

Am. J. Med. Sci. Innov.

View full text Add to dashboard Cite

show abstract

“…Finally, we could identify gene hits from the GO category of the ‘blood vessel endothelial cell migration’ pathway: these included the already-found ATP2B4 and COX2 genes, but also Neurofibromin1 ( NF1 ), a gene mutated in neurofibromatosis 1 patients, who have a higher risk of developing PE and IUGR ( 131 ). The correlation of the identified GO categories and target genes with the examined PE disease subtype supports the relevance of the identified small RNA species in the circulating exosomes.…”

Section: Discussionmentioning

confidence: 99%

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

Gál,

Fóthi,

Orosz

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionPreeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR.MethodsWe isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis.ResultsOverall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR.DiscussionOur rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

show abstract

A Systematic Review of Methods and Practice for Integrating Maternal, Fetal, and Child Health Outcomes, and Family Spillover Effects into Cost-Utility Analyses

Lamsal,

Yeh,

Pullenayegum

et al. 2024

PharmacoEconomics

View full text Add to dashboard Cite

Background Maternal-perinatal interventions delivered during pregnancy or childbirth have unique characteristics that impact the health-related quality of life (HRQoL) of the mother, fetus, and newborn child. However, maternal-perinatal cost-utility analyses (CUAs) often only consider either maternal or child health outcomes. Challenges include, but are not limited to, measuring fetal, newborn, and infant health outcomes, and assessing their impact on maternal HRQoL. It is also important to recognize the impact of maternal-perinatal health on family members’ HRQoL (i.e., family spillover effects) and to incorporate these effects in maternal-perinatal CUAs. Objective The aim was to systematically review the methods used to include health outcomes of pregnant women, fetuses, and children and to incorporate family spillover effects in maternal-perinatal CUAs. Methods A literature search was conducted in Medline, Embase, EconLit, Cochrane Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL), International Network of Agencies for Health Technology Assessment (INAHTA), and the Pediatric Economic Database Evaluation (PEDE) databases from inception to 2020 to identify maternal-perinatal CUAs that included health outcomes for pregnant women, fetuses, and/or children. The search was updated to December 2022 using PEDE. Data describing how the health outcomes of mothers, fetuses, and children were measured, incorporated, and reported along with the data on family spillover effects were extracted. Results Out of 174 maternal-perinatal CUAs identified, 62 considered the health outcomes of pregnant women, and children. Among the 54 quality-adjusted life year (QALY)-based CUAs, 12 included fetal health outcomes, the impact of fetal loss on mothers’ HRQoL, and the impact of neonatal demise on mothers’ HRQoL. Four studies considered fetal health outcomes and the effects of fetal loss on mothers’ HRQoL. One study included fetal health outcomes and the impact of neonatal demise on maternal HRQoL. Furthermore, six studies considered the impact of neonatal demise on maternal HRQoL, while four included fetal health outcomes. One study included the impact of fetal loss on maternal HRQoL. The remaining 26 only included the health outcomes of pregnant women and children. Among the eight disability-adjusted life year (DALY)-based CUAs, two measured fetal health outcomes. Out of 174 studies, only one study included family spillover effects. The most common measurement approach was to measure the health outcomes of pregnant women and children separately. Various approaches were used to assess fetal losses in terms of QALYs or DALYs and their impact on HRQoL of mothers. The most common integration approach was to sum the QALYs or DALYs for pregnant women and children. Most studies reported combined QALYs and incremental QALYs, or DALYs and incremental DALYs, at the family level for pregnant women and children. ...

show abstract

Preimplantation genetic testing for Neurofibromatosis type 1: more than 20 years of clinical experience

Cited by 7 publications

References 47 publications

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

A Systematic Review of Methods and Practice for Integrating Maternal, Fetal, and Child Health Outcomes, and Family Spillover Effects into Cost-Utility Analyses

Contact Info

Product

Resources

About