Adaptive nanopore sequencing to determine pathogenicity of BRCA1 exonic duplication
This study provides a proof-of-concept that nanopore adaptive sampling is a highly efficient technique for the investigation of structural variants of tumour suppressor genes in a clinical context. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Filser, M., Schwartz, M., Merchadou, K., Hamza, A., Villy, M.-C., Decees, A., Frouin, E., Girard, E., Caputo, S. M., Renault, V., Becette, V., Golmard, L., Servant, N., Stoppa-Lyonnet, D., Delattre, O., Colas, C., Masliah-Planchon, J. Tags: Open access Cancer genetics Source Type: research
MSH3: a confirmed predisposing gene for adenomatous polyposis
Conclusion
This report lends further credence to biallelic MSH3 germline pathogenic variants being involved in colorectal and duodenal adenomatous polyposis. Large-scale studies may help clarify the tumour spectrum and associated risks. Ascertainment of EMAST may help with the interpretation of variants of unknown significance. We recommend adding MSH3 to dedicated diagnostic gene panels. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Villy, M.-C., Masliah-Planchon, J., Schnitzler, A., Delhomelle, H., Buecher, B., Filser, M., Merchadou, K., Golmard, L., Melaabi, S., Vacher, S., Blanluet, M., Suybeng, V., Corsini, C., Dhooge, M., Hamzaoui, N., Farelly, S., Ait Omar, A., Benamouzig, R., Tags: Cancer genetics Source Type: research
Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel
Conclusions
Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Levi, H., Carmi, S., Rosset, S., Yerushalmi, R., Zick, A., Yablonski-Peretz, T., The BCAC Consortium, Wang, Q., Bolla, M. K., Dennis, J., Michailidou, K., Lush, M., Ahearn, T., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Arndt, V., Augustinsson, A Tags: Open access Cancer genetics Source Type: research
Newborn screening for primary carnitine deficiency: who will benefit? - a retrospective cohort study
Conclusion
The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Crefcoeur, L., Ferdinandusse, S., van der Crabben, S. N., Dekkers, E., Fuchs, S. A., Huidekoper, H., Janssen, M., Langendonk, J., Maase, R., de Sain, M., Rubio, E., van Spronsen, F. J., Vaz, F. M., Verschoof, R., de Vries, M., Wijburg, F., Visser, G., Lan Tags: Open access Screening Source Type: research
Genetic features and kidney morphological changes in women with X-linked Alport syndrome
Conclusions
The high frequency of de novo variants carried by women indicates that the lack of family history tends to make them susceptible to be underdiagnosed. Coinherited podocyte-related genes are potential contributors to the heterogeneous phenotype of some women. Furthermore, the association between the degree of GBM lesions and decline in kidney function is valuable in evaluating the prognosis for patients with XLAS. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Di, H., Wang, Q., Liang, D., Zhang, J., Gao, E., Zheng, C., Yu, X., Liu, Z. Tags: Genotype-phenotype correlations Source Type: research
Ureteropelvic junction obstruction with primary lymphoedema associated with CELSR1 variants
Conclusion
PL associated with a renal anomaly suggests a CELSR1-related cause. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Alpaslan, M., Mestre-Godin, S., Lay, A., Giacalone, G., Helaers, R., Adham, S., Kovacsik, H., Guillemard, S., Mercier, E., Boon, L., Revencu, N., Brouillard, P., Quere, I., Vikkula, M. Tags: Genotype-phenotype correlations Source Type: research
The Phenotypic variability of 16p11.2 distal BP2-BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples
Conclusion
In this family, the phenotypes observed are most likely caused by the 16p11.2 distal deletion. The lack of other overt pathogenic mutations identified by genomic sequencing reinforces the variable expressivity that should be heeded in a clinical setting. Importantly, distal 16p11.2 deletions can present with a highly variable phenotype even within a single family. Our additional data curation provides further evidence on the variable clinical presentation among those with pathogenetic 16p11.2 (BP2–BP3) mutations. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Woodbury-Smith, M., DAbate, L., Stavropoulos, D. J., Howe, J., Drmic, I., Hoang, N., Zarrei, M., Trost, B., Iaboni, A., Anagnostou, E., Scherer, S. W. Tags: Open access Genotype-phenotype correlations Source Type: research
Exploring the association between congenital vertebral malformations and neural tube defects
Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in somitogenesis and neurulation. Somitogenesis and neurulation rely on factors secreted from neighbouring tissues and the integrity of the axial structure. Crucial signalling pathways like Wnt, Notch and planar cell polarity regulate somitogenesis and neurulation with significant crosstalk. While previous studies suggest an association between CVMs and NTDs, the exact mechanism underlying this relationship remains unclear. In this review, we explore embryoni...
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Ye, Y., Zhang, J., Feng, X., Chen, C., Chang, Y., Qiu, G., Wu, Z., Zhang, T. J., Gao, B., Wu, N. Tags: Review Source Type: research
Time to treat the climate and nature crisis as one indivisible global health emergency
Over 200 health journals call on the United Nations (UN), political leaders and health professionals to recognise that climate change and biodiversity loss are one indivisible crisis and must be tackled together to preserve health and avoid catastrophe. This overall environmental crisis is now so severe as to be a global health emergency. The world is currently responding to the climate crisis and the nature crisis as if they were separate challenges. This is a dangerous mistake. The 28th Conference of the Parties (COP) on climate change is about to be held in Dubai while the 16th COP on biodiversity is due to be held in T...
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Zielinski, C., on behalf of the authorship group listed below Tags: Open access Editorial Source Type: research
Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia
Conclusion
Our results suggest a critical role for SENP7 in nervous system development, haematopoiesis and immune function in humans. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Samra, N., Jansen, N. S., Morani, I., Kakun, R. R., Zaid, R., Paperna, T., Garcia-Dominguez, M., Viner, Y., Frankenthal, H., Shinwell, E. S., Portnov, I., Bakry, D., Shalata, A., Shapira Rootman, M., Kidron, D., Claessens, L. A., Wevers, R. A., Mandel, H. Tags: Novel disease loci Source Type: research
Biallelic variants in DNA2 cause poikiloderma with congenital cataracts and severe growth failure reminiscent of Rothmund-Thomson syndrome
We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2, with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2 were previously associated with microcephalic ost...
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Di Lazzaro Filho, R., Yamamoto, G. L., Silva, T. J., Rocha, L. A., Linnenkamp, B. D. W., Castro, M. A. A., Bartholdi, D., Schaller, A., Leeb, T., Kelmann, S., Utagawa, C. Y., Steiner, C. E., Steinmetz, L., Honjo, R. S., Kim, C. A., Wang, L., Abourjaili-Bi Tags: Novel disease loci Source Type: research
Congenital mirror movements are associated with defective polymerisation of RAD51
Conclusion
Our study demonstrates that RAD51 haploinsufficiency, including loss-of-function of non-truncating variants, results in CMM. The incomplete penetrance likely results from post-transcriptional compensation. Changes in RAD51 levels and/or polymerisation properties could influence guidance of the corticospinal axons during development. Our findings open up new perspectives to understand the role of RAD51 in neurodevelopment. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Trouillard, O., Dupaigne, P., Dunoyer, M., Doulazmi, M., Herlin, M. K., Frismand, S., Riou, A., Legros, V., Chevreux, G., Veaute, X., Busso, D., Fouquet, C., Saint-Martin, C., Meneret, A., Trembleau, A., Dusart, I., Dubacq, C., Roze, E. Tags: Neurogenetics Source Type: research
HnRNPR strongly represses splicing of a critical exon associated with spinal muscular atrophy through binding to an exonic AU-rich element
Conclusion
We identified a novel mechanism that contributes to mis-splicing of SMN2 exon 7. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Jiang, T., Qu, R., Liu, X., Hou, Y., Wang, L., Hua, Y. Tags: Neurogenetics Source Type: research
Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay
Conclusion
This study is the first to describe dominant negative IKZF2 variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Mohajeri, A., Vaseghi-Shanjani, M., Rosenfeld, J. A., Yang, G. X., Lu, H., Sharma, M., Lin, S., Salman, A., Waqas, M., Sababi Azamian, M., Worley, K. C., Del Bel, K. L., Kozak, F. K., Rahmanian, R., Biggs, C. M., Hildebrand, K. J., Lalani, S. R., Nicholas Tags: Developmental defects Source Type: research
Biallelic truncating variants in VGLL2 cause syngnathia in humans
Conclusion
Our results suggest that although loss of VGLL2 leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Agostini, V., Tessier, A., Djaziri, N., Khonsari, R. H., Galliani, E., Kurihara, Y., Honda, M., Kurihara, H., Hidaka, K., Tuncbilek, G., Picard, A., Konas, E., Amiel, J., Gordon, C. T. Tags: Developmental defects Source Type: research
