Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer
Conclusions
Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Fernandez-Castillejo, S., Roig, B., Mele, M., Serrano, S., Salvat, M., Querol, M., Brunet, J., Pineda, M., Cisneros, A., Parada, D., Badia, J., Borras, J., Rodriguez-Balada, M., Guma, J. Tags: Open access Cancer genetics Source Type: research
Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes
Conclusion
Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Carvalho, N. d. A. d., Santiago, K. M., Maia, J. M. L., Costa, F. D., Formiga, M. N., Soares, D. C. d. Q., Paixao, D., Mello, C. A. L. d., Costa, C. M. L. d., Rocha, J. C. C. d., Rivera, B., Carraro, D. M., Torrezan, G. T. Tags: Open access Cancer genetics Source Type: research
Experience of reassessing FBN1 variants of uncertain significance by gene-specific guidelines
Conclusions
After reassessing FBN1 variants according to FBN1-specific guideline and up-to-date database, a significant number of VUS was reclassified. Clinical laboratories are encouraged to perform variant reassessment at regular intervals or when there is a major change in the principle of variant interpretation. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Yoon, E., Lee, J. K., Park, T. K., Chang, S.-A., Huh, J., Kim, J.-W., Kim, D.-K., Jang, J.-H. Tags: Diagnostics Source Type: research
Integrating RNA-Seq into genome sequencing workflow enhances the analysis of structural variants causing neurodevelopmental disorders
Conclusion
Our study confirmed that GS significantly improves the diagnostic performance of NDDs. However, most variants detectable by GS alone are structural or located in non-coding regions, which can pose challenges for interpretation. Integration of RNA-Seq data overcame this limitation by confirming the impact of variants at the transcriptional or regulatory level. This result paves the way for new routinely applicable diagnostic protocols. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Riquin, K., Isidor, B., Mercier, S., Nizon, M., Colin, E., Bonneau, D., Pasquier, L., Odent, S., Le Guillou Horn, X. M., Le Guyader, G., Toutain, A., Meyer, V., Deleuze, J.-F., Pichon, O., Doco-Fenzy, M., Bezieau, S., Cogne, B. Tags: Diagnostics Source Type: research
Multiple molecular diagnoses in the field of intellectual disability and congenital anomalies: 3.5% of all positive cases
Conclusion
MMDs are frequent in CA/ID and remain a strong challenge. Reanalysis of positive ES data appears essential when phenotypes are partially explained by the initial diagnosis or atypically enriched overtime. Up-to-date clinical data, clinical expertise from the referring physician, strong interactions between clinicians and biologists, and increasing gene discoveries and improved ES bioinformatics tools appear all the more fundamental to enhance chances of identifying MMDs. It is essential to provide appropriate patient care and genetic counselling. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Racine, C., Denomme-Pichon, A.-S., Engel, C., Tran Mau-them, F., Bruel, A.-L., Vitobello, A., Safraou, H., Sorlin, A., Nambot, S., Delanne, J., Garde, A., Colin, E., Moutton, S., Thevenon, J., Jean-Marcais, N., Willems, M., Genevieve, D., Pinson, L., Perr Tags: Diagnostics Source Type: research
Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients
Conclusions
STAR and NR0B1 were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Duan, Y., Zheng, W., Xia, Y., Zhang, H., Liang, L., Wang, R., Yang, Y., Zhang, K., Lu, D., Sun, Y., Han, L., Yu, Y., Gu, X., Sun, Y., Xiao, B., Qiu, W. Tags: Diagnostics Source Type: research
Genotype-phenotype associations in Alström syndrome: a systematic review and meta-analysis
Conclusion
Pathogenic variants in exon 10 of the ALMS1 gene were associated with a higher prevalence of liver disease. However, the location of the variant in the ALMS1 gene does not have a major impact on the phenotype developed by the patient. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Bea-Mascato, B., Valverde, D. Tags: Open access Genotype-phenotype correlations Source Type: research
Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases
Conclusion
There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Liang, L., Ling, S., Yu, Y., Shuai, R., Qiu, W., Zhang, H., Shen, L., Wu, S., Wei, H., Chen, Y., Yang, C., Xu, P., Chen, X., Zou, H., Feng, J., Niu, T., Hu, H., Gong, Z., Chen, T., Zhan, X., Gu, X., Han, L. Tags: Genotype-phenotype correlations Source Type: research
Carriers of autosomal recessive conditions: are they really 'unaffected?
Mendel’s Law of Dominance suggests that recessive disease expression requires the inheritance of two mutated alleles as the dominant, wildtype allele suppresses disease presentation leading to the expression of physiological normal phenotypes. However, there is existing evidence that challenges this school of thought. Here, we summarise existing literature evaluating metabolic and health impacts among carriers of autosomal recessive conditions, focusing on phenylketonuria (PKU), classical homocystinuria, galactosemia and Usher syndrome as examples. Our findings suggest that carriers, often described as ‘unaffec...
Source: Journal of Medical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Hames, A., Khan, S., Gilliland, C., Goldman, L., Lo, H. W., Magda, K., Keathley, J. Tags: Review Source Type: research
A multilayered approach to the analysis of genetic data from individuals with suspected albinism
Albinism is a clinically and genetically heterogeneous group of conditions characterised by visual abnormalities and variable degrees of hypopigmentation. Multiple studies have demonstrated the clinical utility of genetic investigations in individuals with suspected albinism. Despite this, the variation in the provision of genetic testing for albinism remains significant. One key issue is the lack of a standardised approach to the analysis of genomic data from affected individuals. For example, there is variation in how different clinical genetic laboratories approach genotypes that involve incompletely penetrant alleles, ...
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Sergouniotis, P. I., Michaud, V., Lasseaux, E., Campbell, C., Plaisant, C., Javerzat, S., Birney, E., Ramsden, S. C., Black, G. C., Arveiler, B. Tags: Open access Vision science Source Type: research
Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project
Conclusion
Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Moore, A. R., Yu, J., Pei, Y., Cheng, E. W. Y., Taylor Tavares, A. L., Walker, W. T., Thomas, N. S., Kamath, A., Ibitoye, R., Josifova, D., Wilsdon, A., Ross, A., Calder, A. D., Offiah, A. C., Wilkie, A. O. M., Genomics England Research Consortium, Taylor Tags: Open access Diagnostics Source Type: research
Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
Conclusion
This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of ANKRD11 variants in skeletal and brain development. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Peluso, F., Caraffi, S. G., Contro, G., Valeri, L., Napoli, M., Carboni, G., Seth, A., Zuntini, R., Coccia, E., Astrea, G., Bisgaard, A.-M., Ivanovski, I., Maitz, S., Brischoux-Boucher, E., Carter, M. T., Dentici, M. L., Devriendt, K., Bellini, M., Digili Tags: Open access Phenotypes Source Type: research
Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes
Conclusion
This study adds evidence that MIPOGG is an appropriate tool for CPS screening in clinical practice. MIPOGG’s strength is that it starts with a specific cancer diagnosis and incorporates criteria relevant for associated CPSs, making MIPOGG a more universally accessible diagnostic adjunct that does not require in-depth knowledge of each CPS. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Hebert, R., Cullinan, N., Armstrong, L., Blood, K. A., Brossard, J., Brunga, L., Cacciotti, C., Caswell, K., Cellot, S., Coltin, H., Deyell, R. J., Felton, K., Fernandez, C. V., Fleming, A. J., Gibson, P., Hammad, R., Jabado, N., Johnston, D. L., Lafay-Co Tags: Clinical guidelines Source Type: research
CHEK2 is not a Li-Fraumeni syndrome gene: time to update public resources
The gene-disease relationship for CHEK2 remains listed as ‘Li-Fraumeni syndrome 2’ in public resources such as OMIM and MONDO, despite published evidence to the contrary, causing frustration among Li-Fraumeni syndrome (LFS) clinical experts. Here, we compared personal cancer characteristics of 2095 CHEK2 and 248 TP53 pathogenic variant carriers undergoing multigene panel testing at Ambry Genetics against 15 135 individuals with no known pathogenic variant. Our results from a within-cohort logistic regression approach highlight obvious differences between clinical presentation of TP53 and CHEK2 pathogenic varian...
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Fortuno, C., Richardson, M., Pesaran, T., Yussuf, A., Horton, C., James, P. A., Spurdle, A. B. Tags: Cancer genetics Source Type: research
Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt-Hogg-Dube syndrome
To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt–Hogg–Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fuma...
Source: Journal of Medical Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Pan, H.-H., Ruan, D.-D., Wu, M., Chen, T., Lu, T., Gan, Y.-M., Wang, C., Liao, L.-S., Lin, X.-F., Chen, X., Zhu, Y.-B., Fang, Z.-T., Yu, Q.-H., Yang, G.-K., Ye, L.-F., Luo, J.-W. Tags: Cancer genetics Source Type: research
