Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement
Conclusion
Our findings show that pathogenic variants in MAN2A2 cause a novel autosomal recessive CDG with neurological involvement and facial dysmorphism. Here, we also present the development of a cell-based complementation assay to assess the pathogenicity of MAN2A2 variants, which can also be extended to MAN2A1 variants for future diagnosis. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - June 21, 2023 Category: Genetics & Stem Cells Authors: Mahajan, S., Ng, B. G., AlAbdi, L., Earnest, P. D. J., Sosicka, P., Patel, N., Helaby, R., Abdulwahab, F., He, M., Alkuraya, F. S., Freeze, H. H. Tags: Genotype-phenotype correlations Source Type: research
OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum
Conclusions
Our results indicate that proper OTX2 dosage seems to be critical for the normal development of the first and second branchial arches. Overall, we demonstrated that OTX2 genomic duplications are a recurrent cause of OAVS marked by auricular malformations of variable severity. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Celse, T., Tingaud-Sequeira, A., Dieterich, K., Siegfried, G., Lecaignec, C., Bouneau, L., Fannemel, M., Salaun, G., Laffargue, F., Martinez, G., Satre, V., Vieville, G., Bidart, M., Soussi Zander, C., Turesson, A.-C., Splitt, M., Reboul, D., Chiesa, J., Tags: Copy-number variation Source Type: research
Genetic diagnosis of Duchenne and Becker muscular dystrophy through mRNA analysis: new splicing events
Conclusion
These findings indicate that mRNA analysis of the DMD gene is a valuable tool to reach a precise genetic diagnosis in patients with a clinical and anatomopathological suspicion of dystrophinopathy that remain genetically undiagnosed after routine genetic testing. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Segarra-Casas, A., Dominguez-Gonzalez, C., Hernandez-Lain, A., Sanchez-Calvin, M. T., Camacho, A., Rivas, E., Campo-Barasoain, A., Madruga, M., Ortez, C., Natera-de Benito, D., Nascimento, A., Codina, A., Rodriguez, M. J., Gallano, P., Gonzalez-Quereda, L Tags: Open access Diagnostics Source Type: research
Reporting clinically relevant genetic variants unrelated to genomic test requests: a survey of Australian clinical laboratory policies and practices
We present recommendations for consideration when developing laboratory policies. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Tudini, E., Haas, M. A., Mattiske, T., Spurdle, A. B. Tags: Diagnostics Source Type: research
In-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2
Conclusions
Although we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of FOXP2 dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce that FOXP2 provides a valuable entry point for examining the neurobiological bases of speech disorder. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Morison, L. D., Meffert, E., Stampfer, M., Steiner-Wilke, I., Vollmer, B., Schulze, K., Briggs, T., Braden, R., Vogel, A., Thompson-Lake, D., Patel, C., Blair, E., Goel, H., Turner, S., Moog, U., Riess, A., Liegeois, F., Koolen, D. A., Amor, D. J., Kleefs Tags: Open access Cognitive and behavioural genetics Source Type: research
X-linked variations in SHROOM4 are implicated in congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems
Conclusion
The identified SNVs and CNVs in affected individuals with congenital anomalies of the urinary tract, the anorectal, the cardiovascular and the central nervous systems, and subsequent embryonic mouse and zebrafish studies suggest SHROOM4 as a developmental gene for different organ systems. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Kolvenbach, C. M., Felger, T., Schierbaum, L., Thiffault, I., Pastinen, T., Szczepanska, M., Zaniew, M., Adamczyk, P., Bayat, A., Yilmaz, O., Lindenberg, T. T., Thiele, H., Hildebrandt, F., Hinderhofer, K., Moog, U., Hilger, A. C., Sullivan, B., Bartik, L Tags: Open access Developmental defects Source Type: research
New insights into CC2D2A-related Joubert syndrome
Conclusion
This study contradicts previous literature stating an association between CC2D2A-related JS and ventriculomegaly. Our study implies that CC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Harion, M., Qebibo, L., Riquet, A., Rougeot, C., Afenjar, A., Garel, C., Louha, M., Lacaze, E., Audic-Gerard, F., Barth, M., Berquin, P., Bonneau, D., Bourdain, F., Busa, T., Colin, E., Cuisset, J.-M., Des Portes, V., Dorison, N., Francannet, C., Heron, B Tags: Neurogenetics Source Type: research
MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1
Referenced paragraph The genetic cause of very young onset ovarian cancer (VYOC), diagnosed under 30 years of age, is unclear.1 The histology and underlying genetics in VYOC is significantly different from the overall epithelial ovarian cancer (EOC) population; we aimed to explore this in VYOC cases known to the North-West of England. We found mismatch repair genes to be the most commonly affected in VYOCs, especially MSH2. The cumulative likelihood of an EOC in MSH2 heterozygotes is >2% by age 35, with this likelihood still below 0.5% for BRCA1 and rare for BRCA2.2 Article The inherited landscape of epithelial ovarian ...
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Flaum, N., Crosbie, E. J., Woodward, E. R., Lalloo, F., Morgan, R., Ryan, N., Evans, D. G. Tags: Open access Cancer genetics Source Type: research
Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines
Conclusions
The development and evolution of CDH1-specific criteria by the expert panel resulted in decreased uncertain and conflicting interpretations of variants in this clinically actionable gene, which can ultimately lead to more effective clinical management recommendations. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Luo, X., Maciaszek, J. L., Thompson, B. A., Leong, H. S., Dixon, K., Sousa, S., Anderson, M., Roberts, M. E., Lee, K., Spurdle, A. B., Mensenkamp, A. R., Brannan, T., Pardo, C., Zhang, L., Pesaran, T., Wei, S., Fasaye, G.-A., Kesserwan, C., Shirts, B. H., Tags: Cancer genetics Source Type: research
Germline mutations in WNK2 could be associated with serrated polyposis syndrome
Conclusion
After whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the WNK2 gene. Functional studies suggested germline WNK2 variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Soares de Lima, Y., Arnau-Collell, C., Munoz, J., Herrera-Pariente, C., Moreira, L., Ocana, T., Diaz-Gay, M., Franch-Exposito, S., Cuatrecasas, M., Carballal, S., Lopez-Novo, A., Moreno, L., Fernandez, G., Diaz de Bustamante, A., Peters, S., Sommer, A. K. Tags: Open access Cancer genetics Source Type: research
Recurring germline mosaicism in a family due to reversion of an inherited derivative chromosome 8 from an 8;21 translocation with interstitial telomeric sequences
Conclusion
Mosaicism in the proband, his half-sister and half-cousin resulting from loss of chromosome 21 material from the der(8) appears to be a postzygotic event due to the genomic instability of ITS and associated with selective growth advantage of normal cells. The reversion of the inherited der(8) to a normal chromosome 8 in this family resembles revertant mosaicism of point mutations. We propose that ITS could mediate recurring revertant mosaicism for some constitutional chromosomal structural abnormalities. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Bi, W., Yuan, B., Liu, P., Murry, J. B., Qin, X., Xia, F., Quach, T., Cooper, L. M., Wiszniewska, J., Hixson, P., Peacock, S., Tonk, V. S., Huff, R. W., Ortega, V., Lupski, J. R., Scherer, S. E., Littlejohn, R. O., Velagaleti, G. V. N., Roeder, E. R., Che Tags: Chromosomal rearrangements Source Type: research
Experience using singleton exome sequencing of probands as an approach to preconception carrier screening in consanguineous couples
Conclusions
Our results demonstrate that ES outperforms panel-based screening in a PCS context in consanguineous couples and could potentially increase their reproductive autonomy and facilitate informed decision-making. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Abuli, A., Costa-Roger, M., Codina-Sola, M., Valenzuela, I., Leno-Colorado, J., Rovira-Moreno, E., Cueto-Gonzalez, A., Fernandez-Alvarez, P., Garcia-Arumi, E., Cusco, I., Tizzano, E. F. Tags: Screening Source Type: research
Systems approach to enhance Lynch syndrome diagnosis through tumour testing
Conclusion
Implementation of systematic case identification and referral support mechanisms significantly increased the proportion of patients undergoing genetic testing and doubled the percentage of patients diagnosed with LS with no referral differences across racial/ethnic groups. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Singh, V., Mezzacappa, C., Gershkovich, P., Di Giovanna, J., Ganzak, A., Gibson, J., Sinard, J., Xicola, R. M., Llor, X. Tags: Screening Source Type: research
Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)
Purpose and scope
The aim of this position statement is to provide recommendations for clinicians regarding the use of genetic and metabolic investigations for patients with neurodevelopmental disorders (NDDs), specifically, patients with global developmental delay (GDD), intellectual disability (ID) and/or autism spectrum disorder (ASD). This document also provides guidance for primary care and non-genetics specialists caring for these patients while awaiting consultation with a clinical geneticist or metabolic specialist.
Methods of statement development
A multidisciplinary group reviewed existing literature and guideli...
Source: Journal of Medical Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Carter, M. T., Srour, M., Au, P.-Y. B., Buhas, D., Dyack, S., Eaton, A., Inbar-Feigenberg, M., Howley, H., Kawamura, A., Lewis, S. M. E., McCready, E., Nelson, T. N., Vallance, H., on behalf of the Canadian College of Medical Geneticists Tags: Open access Position statement Source Type: research
Clinical, neuroimaging and molecular characteristics of PPP2R5D-related neurodevelopmental disorders: an expanded series with functional characterisation and genotype-phenotype analysis
Conclusion
Our study delineates the most common features of PPP2R5D-related neurodevelopmental disorders, expands the clinical and molecular spectrum and identifies genotype–phenotype correlations. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - April 20, 2023 Category: Genetics & Stem Cells Authors: Oyama, N., Vaneynde, P., Reynhout, S., Pao, E. M., Timms, A., Fan, X., Foss, K., Derua, R., Janssens, V., Chung, W., Mirzaa, G. M. Tags: Neurogenetics Source Type: research
