Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects
We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Gibb, J., Wall, E., Fields, E., Seale, A., Armstrong, C., Bamber, A., Daubeney, P., Jacobs-Pearson, M., Marton, T., Stals, K., Low, K., Kaski, J. P., Spentzou, G. Tags: Phenotypes Source Type: research
Clinical phenotype of FOXP1 syndrome: parent-reported medical signs and symptoms in 40 individuals
Conclusion
The results of this study may be used to further guide medical management and identify patient priorities for future research targeted on those features of FOXP1 syndrome that most impair quality of life of patients and their families. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Koene, S., Ropers, F. G., Wieland, J., Rybak, T., Wildschut, F., Berghuis, D., Morgan, A., Trelles, M. P., Scheepe, J. R., Bökenkamp, R., Peeters-Scholte, C. M. P. C. D., Braden, R., Santen, G. W. E. Tags: Phenotypes Source Type: research
Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO
Conclusion
Overall, the insurance coverage for HBOC patients with BC has increased the frequency of RRSO in Japan. However, a comparison between the number of probands and family members indicated that the diagnosis among family members is inadequate. The inequality in the use of genetic services by socioeconomic groups is an issue of further concern. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Abe, A., Nomura, H., Fusegi, A., Yunokawa, M., Ueki, A., Habano, E., Arakawa, H., Kaneko, K., Minoura, Y., Inari, H., Ueno, T., Kanao, H. Tags: Open access Cancer genetics Source Type: research
Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400
Conclusion
PGVs in BRCA1 are associated with G3_TNBCs. Familial TNBCs and isolated TNBCs <30 years have a >10% likelihood of a PGV in BRCA1. BRCA1_PGVs are associated with younger age of familial TNBC. There was no evidence for any increased risk of TNBC with CHEK2 or ATM PGVs. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Woodward, E. R., Lalloo, F., Forde, C., Pugh, S., Burghel, G. J., Schlecht, H., Harkness, E. F., Howell, A., Howell, S. J., Gandhi, A., Evans, D. G. Tags: Cancer genetics Source Type: research
Update of the UMD-VHL database: classification of 164 challenging variants based on genotype-phenotype correlation among 605 entries
Conclusion
Consequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Mougel, G., Mohamed, A., Burnichon, N., Giraud, S., Pigny, P., Bressac-de Paillerets, B., Mirebeau-Prunier, D., Buffet, A., Savagner, F., Romanet, P., Arlot, Y., Gardie, B., Gimenez-Roqueplo, A.-P., Beroud, C., Richard, S., Barlier, A. Tags: Cancer genetics Source Type: research
Titin copy number variations associated with dominant inherited phenotypes
Conclusion
Identifying TTN CNVs will further increase diagnostic sensitivity in these complex neuromuscular pathologies. Our cohort of patients enabled us to identify new deletion-type CNVs in the TTN gene, with unexpected autosomal dominant transmission. This is valuable in establishing new genotype–phenotype associations of titinopathies, mainly distal myopathy in most of the patients. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Perrin, A., Metay, C., Savarese, M., Ben Yaou, R., Demidov, G., Nelson, I., Sole, G., Pereon, Y., Bertini, E. S., Fattori, F., D'Amico, A., Ricci, F., Ginsberg, M., Seferian, A., Boespflug-Tanguy, O., Servais, L., Chapon, F., Lagrange, E., Gaudon, K., Blo Tags: Copy-number variation Source Type: research
Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis
Conclusion
Our data expand the spectrum of variants and phenotypic spectrum associated with homozygous variants of SMAD6 to include craniosynostosis. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Luyckx, I., Walton, I. S., Boeckx, N., Van Schil, K., Pang, C., De Praeter, M., Lord, H., Watson, C. M., Bonthron, D. T., Van Laer, L., Wilkie, A. O. M., Loeys, B. Tags: Open access Genotype-phenotype correlations Source Type: research
Neuromuscular and cardiovascular phenotypes in paediatric titinopathies: a multisite retrospective study
Conclusion
Our cohort demonstrates the genotype–phenotype spectrum of paediatric-onset titinopathies identified in clinical practice and highlights the risk of life-threatening cardiovascular complications. We show the difficulties of obtaining a molecular diagnosis, particularly in neuromuscular patients, and bring awareness to the complexities of genetic counselling in this population. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Meyer, A. P., Barnett, C. L., Myers, K., Siskind, C. E., Moscarello, T., Logan, R., Roggenbuck, J., Rich, K. A. Tags: Genotype-phenotype correlations Source Type: research
Heterozygous COL17A1 variants are a frequent cause of amelogenesis imperfecta
Conclusion
These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care. (Sour...
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Hany, U., Watson, C. M., Liu, L., Smith, C. E. L., Harfoush, A., Poulter, J. A., Nikolopoulos, G., Balmer, R., Brown, C. J., Patel, A., Simmonds, J., Charlton, R., Acosta de Camargo, M. G., Rodd, H. D., Jafri, H., Antanaviciute, A., Moffat, M., Al-Jawad, Tags: Open access Genotype-phenotype correlations Source Type: research
Non-coding CGG repeat expansion in LOC642361/NUTM2B-AS1 is associated with a phenotype of oculopharyngodistal myopathy
Conclusions
We identified another two unrelated cases with CGG repeat expansion in the long non-coding RNA of the LOC642361/NUTM2B-AS1 gene, presenting with a phenotype of OPDM. Our cases broadened the recognised phenotypic spectrum and pathogenesis in the disease associated with CGG repeat expansion in LOC642361/NUTM2B-AS1. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Gu, X., Yu, J., Jiao, K., Deng, J., Xia, X., Qiao, K., Yue, D., Gao, M., Zhao, C., Dong, J., Huang, G., Shan, J., Yan, C., Di, L., Da, Y., Zhu, W., Xi, J., Wang, Z. Tags: Neurogenetics Source Type: research
Familial Alzheimers disease associated with heterozygous NPC1 mutation
We describe a novel NPC1 heterozygous mutation harboured by different members of a family with autosomal dominant late-onset amnesic AD without NPC-associated features. A missense mutation in homozygous state in the same aminoacidic position has been previously reported in a patient with NPC with severe phenotype. The alteration of serum oxysterols in our family corroborates the pathogenic role of our NPC1 mutation. Our work, illustrating clinical and biochemical disease hallmarks associated with NPC1 heterozygosity in patients affected by AD, provides relevant insights into the pathogenetic mechanisms underlying this poss...
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Lopergolo, D., Bianchi, S., Gallus, G. N., Locci, S., Pucci, B., Leoni, V., Gasparini, D., Tardelli, E., Chincarini, A., Sestini, S., Santorelli, F. M., Zetterberg, H., De Stefano, N., Mignarri, A. Tags: Neurogenetics Source Type: research
Novel TFG mutation causes autosomal-dominant spastic paraplegia and defects in autophagy
Conclusions
Our findings suggest that autophagy impairment may serve as a common pathomechanism among different clinical phenotypes caused by TFG mutations. Consequently, targeting autophagy may facilitate the development of a uniform treatment for TFG-related neurological disorders. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Xu, L., Wang, Y., Wang, W., Zhang, R., Zhao, D., Yun, Y., Liu, F., Zhao, Y., Yan, C., Lin, P. Tags: Neurogenetics Source Type: research
De novo variants in KCNJ3 are associated with early-onset epilepsy
Conclusion
Our findings suggest that de novo LOF variants in KCNJ3 are associated with early-onset epilepsy. Genetic testing of KCNJ3 in patients with epilepsy may serve as a strategy for precision medicine. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Li, J., Mei, S., Mao, X., Wan, L., Wang, H., Xiao, B., Song, Y., Gu, W., Liu, Y., Long, L. Tags: Neurogenetics Source Type: research
Ancestry, race and ethnicity: the role and relevance of language in clinical genetics practice
Conclusion
There are many challenges around the use and utility of these terms. Currently, genomic databases are populated primarily with data from people of European descent, and this can lead to health disparities and poorer service for minoritised or underserved populations. Sensitivity and consideration are needed when communicating with patients around these areas. We explore the role and relevance of language around biological lineage in clinical genetics practice. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Redman, M. G., Horton, R. H., Carley, H., Lucassen, A. Tags: Open access Ethics and policy Source Type: research
Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey
Conclusion
The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Allen, S., Loong, L., Garrett, A., Torr, B., Durkie, M., Drummond, J., Callaway, A., Robinson, R., Burghel, G. J., Hanson, H., Field, J., McDevitt, T., McVeigh, T. P., Bedenham, T., Bowles, C., Bradshaw, K., Brooks, C., Butler, S., Del Rey Jimenez, J. C., Tags: Open access Clinical guidelines Source Type: research
