Long-term tumour dormancy in a BRCA1 heterozygote
We report a BRCA1 heterozygote who developed a pelvic HGSC 15 years post-RRSO, following an occult Fallopian tube HGSC that was missed on initial pathological examination. Exome sequencing of DNA derived from normal and tumour tissues showed that the pelvic tumour is a recurrence from the original Fallopian tube tumour. BRCA1 and BRCA2 GPVs are the strongest known risk factors for HGSC, and for this reason, RRSO is offered to women who are heterozygous for BRCA1/2 GPVs as standard of care, usually between the ages of 35 and 50 years. For women who have undergone RRSO, there... (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 23, 2022 Category: Genetics & Stem Cells Authors: Amuzu, S., Fu, L., Demko, N., Rivera, B., Domecq, C., de Kock, L., Hamel, N., Gilbert, L., Polak, P., Ragoussis, J., Foulkes, W. D. Tags: Cancer genetics Source Type: research
SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma
Conclusion
SDHB truncating variants convey an elevated risk for development of both PPGL and malignancy compared with missense variants. These results further support earlier robust associations between truncating variants and PPGL, and also suggest that the two variant types differ in their impact on complex II function, with PPGL/HNPGL tissues displaying differing sensitivities to changes in complex II function. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 23, 2022 Category: Genetics & Stem Cells Authors: Bayley, J. P., Bausch, B., Jansen, J. C., Hensen, E. F., van der Tuin, K., Corssmit, E. P., Devilee, P., Neumann, H. P. Tags: Cancer genetics Source Type: research
Diagnostic workup in children with arthrogryposis: description of practices from a single reference centre, comparison with literature and suggestion of recommendations
Conclusion
The aetiological management for patients with AMC remains arduous. This process will be facilitated by the increasing use of next-generation sequencing combined with detailed phenotyping. Invasive investigations should be avoided because of their limited yield. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 23, 2022 Category: Genetics & Stem Cells Authors: Le Tanno, P., Latypova, X., Rendu, J., Faure, J., Bourg, V., Gauthier, M., Billy-Lopez, G., Jouk, P.-S., Dieterich, K. Tags: Clinical guidelines Source Type: research
COP27 climate change conference: urgent action needed for Africa and the world
Wealthy nations must step up support for Africa and vulnerable countries in addressing past, present and future impacts of climate change The 2022 report of the Intergovernmental Panel on Climate Change paints a dark picture of the future of life on earth, characterised by ecosystem collapse, species extinction and climate hazards such as heatwaves and floods.1 These are all linked to physical and mental health problems, with direct and indirect consequences of increased morbidity and mortality. To avoid these catastrophic health effects across all regions of the globe, there is broad agreement—as 231 health journals...
Source: Journal of Medical Genetics - December 23, 2022 Category: Genetics & Stem Cells Authors: Zielinski, C., on behalf of the authorship group listed below Tags: Open access Editorial Source Type: research
Patient-facing digital tools for delivering genetic services: a systematic review
This study systematically reviewed the literature on the impact of digital genetics tools on patient care and system efficiencies. MEDLINE and Embase were searched for articles published between January 2010 and March 2021. Studies evaluating the use of patient-facing digital tools in the context of genetic service delivery were included. Two reviewers screened and extracted patient-reported and system-focused outcomes from each study. Data were synthesised using a descriptive approach. Of 3226 unique studies identified, 87 were included. A total of 70 unique digital tools were identified. As a result of using digital tool...
Source: Journal of Medical Genetics - December 23, 2022 Category: Genetics & Stem Cells Authors: Lee, W., Shickh, S., Assamad, D., Luca, S., Clausen, M., Somerville, C., Tafler, A., Shaw, A., Hayeems, R., Bombard, Y., Genetics Navigator Study Team, Bombard, Hayeems, Aronson, Bernier, Brudno, Carroll, Chad, Clausen, Cohn, Costain, Dhalla, Faghfoury, F Tags: Review Source Type: research
CDKN1C hyperexpression in two patients with severe growth failure and microdeletions affecting the paternally inherited KCNQ1OT1:TSS-DMR
Conclusion
Paternal deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers, disrupt KCNQ1OT1 expression, strongly activate CDKN1C expression and consequently cause severe growth failure. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Hara-Isono, K., Yamazawa, K., Tanaka, S., Nishi, E., Fukami, M., Kagami, M. Tags: Epigenetics Source Type: research
Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases
Conclusion
Combining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Testard, Q., Vanhoye, X., Yauy, K., Naud, M.-E., Vieville, G., Rousseau, F., Dauriat, B., Marquet, V., Bourthoumieu, S., Genevieve, D., Gatinois, V., Wells, C., Willems, M., Coubes, C., Pinson, L., Dard, R., Tessier, A., Herve, B., Vialard, F., Harzallah, Tags: Copy-number variation Source Type: research
Loss of seryl-tRNA synthetase (SARS1) causes complex spastic paraplegia and cellular senescence
Conclusion
We refine the phenotypic spectrum and modes of inheritance of a newly described, ultrarare neurodevelopmental disorder, while unveiling the role of SARS1 as a regulator of cell growth, division and senescence. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Verdura, E., Senger, B., Raspall-Chaure, M., Schlüter, A., Launay, N., Ruiz, M., Casasnovas, C., Rodriguez-Palmero, A., Macaya, A., Becker, H. D., Pujol, A. Tags: Open access Neurogenetics Source Type: research
TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation
Conclusion
The clinical features after CI and physiological expression of TMPRSS3 suggest against a major role of TMPRSS3 in auditory neurons. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Chen, Y.-S., Cabrera, E., Tucker, B. J., Shin, T. J., Moawad, J. V., Totten, D. J., Booth, K. T., Nelson, R. F. Tags: Neurogenetics Source Type: research
Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence
Conclusions
These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Lee, A., Mavaddat, N., Cunningham, A., Carver, T., Ficorella, L., Archer, S., Walter, F. M., Tischkowitz, M., Roberts, J., Usher-Smith, J., Simard, J., Schmidt, M. K., Devilee, P., Zadnik, V., Jürgens, H., Mouret-Fourme, E., De Pauw, A., Rookus, M Tags: Open access Cancer genetics Source Type: research
Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study
Conclusion
The multifactorial BOADICEA model provides valid breast cancer risk predictions and a basis for personalised decision-making on disease prevention and screening. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Yang, X., Eriksson, M., Czene, K., Lee, A., Leslie, G., Lush, M., Wang, J., Dennis, J., Dorling, L., Carvalho, S., Mavaddat, N., Simard, J., Schmidt, M. K., Easton, D. F., Hall, P., Antoniou, A. C. Tags: Open access Cancer genetics Source Type: research
First estimates of diffuse gastric cancer risks for carriers of CTNNA1 germline pathogenic variants
Conclusion
This is the largest series of CTNNA1 families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion of CTNNA1 in germline testing panels. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Coudert, M., Drouet, Y., Delhomelle, H., Svrcek, M., Benusiglio, P. R., Coulet, F., Clark, D. F., Katona, B. W., van Hest, L. P., van der Kolk, L. E., Cats, A., van Dieren, J. M., Nehoray, B., Slavin, T., Spier, I., Hüneburg, R., Lobo, S., Oliveir Tags: Cancer genetics Source Type: research
A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot
Conclusion
Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses.
Trial registration number
ISRCTN87845055. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Torr, B., Jones, C., Choi, S., Allen, S., Kavanaugh, G., Hamill, M., Garrett, A., MacMahon, S., Loong, L., Reay, A., Yuan, L., Valganon Petrizan, M., Monson, K., Perry, N., Fallowfield, L., Jenkins, V., Gold, R., Taylor, A., Gabe, R., Wiggins, J., Lucasse Tags: Open access Cancer genetics Source Type: research
Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms
Conclusions
There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Sena, C., Iannello, G., Skowronski, A. A., Dannheim, K., Cheung, L., Agrawal, P. B., Hirschhorn, J. N., Zeitler, P., LeDuc, C. A., Stratigopoulos, G., Thaker, V. V. Tags: Phenotypes Source Type: research
The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness
FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising dive...
Source: Journal of Medical Genetics - November 22, 2022 Category: Genetics & Stem Cells Authors: Hessl, D., Rosselot, H., Miller, R., Espinal, G., Famula, J., Sherman, S. L., Todd, P. K., Cabal Herrera, A. M., Lipworth, K., Cohen, J., Hall, D. A., Leehey, M., Grigsby, J., Weber, J. D., Alusi, S., Wheeler, A., Raspa, M., Hudson, T., Sobrian, S. K. Tags: Open access Therapeutics Source Type: research
