Genotypes and phenotypes of DNM1 encephalopathy
Conclusion
DNM1-related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Kim, J., Teng, L.-Y., Shaker, B., Na, D., Koh, H. Y., Kwon, S. S., Lee, J. S., Kim, H. D., Kang, H.-C., Kim, S. H. Tags: Genotype-phenotype correlations Source Type: research
Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities
Conclusion
Both lung intrinsic and extrinsic skeletal abnormalities contribute to OI pulmonary dysfunction. Most young adult patients have restrictive disease and abnormal gas exchange; impairment is greater in type III than type IV OI. Decreased FEF25%–75% and thickening of small bronchi walls indicate a critical role for small airways. Lung parenchymal abnormalities (atelectasis, reticulations) and pleural thickening were also detected. Clinical interventions to mitigate these impairments are warranted.
Trial registration number
NCT03575221. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Gochuico, B. R., Hossain, M., Talvacchio, S. K., Zuo, M. X. G., Barton, M., Dang Do, A. N., Marini, J. C. Tags: Genotype-phenotype correlations Source Type: research
Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands
Conclusion
We found an overall higher AF and lower penetrance than previously reported, confirming that DFNA21 is relatively common in the Netherlands. This supports its potential suitability as a target for therapeutic development. Studying possible modifying factors is essential to explain the phenotypical variability and to identify patients eligible for such a therapy. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Velde, H. M., Homans, N. C., Goedegebure, A., Lanting, C. P., Pennings, R. J. E., Kremer, H. Tags: Genotype-phenotype correlations Source Type: research
TP53 c.455C>T p.(Pro152Leu) pathogenic variant is a lower risk allele with attenuated risks of breast cancer and sarcoma
Germline (likely) pathogenic TP53 variants cause Li-Fraumeni syndrome (LFS), typically associated with sarcoma, brain, breast and adrenal tumours. Although classical LFS is highly penetrant, the p.R337H variant, common in Brazil, is typically associated with childhood adrenal tumours and an older onset age of other LFS tumours. Previously, we reported the finding of p.P152L in 6 children from 5 families with adrenal tumours. We have now assessed cancer risks over the subsequent 23 years, and in one further family with p.P152L. Cancer risks were compared with those in the 11 families known to our service with classical domi...
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Evans, D. G., Harkness, E. F., Woodward, E. R. Tags: Cancer genetics Source Type: research
Pancreatic cancer cluster region identified in BRCA2
Pancreatic cancer has a poor prognosis. Lack of diagnostic markers prevents its early diagnosis and treatment. Pathogenic germline variation in BRCA1 and BRCA2 (BRCA) is genetic predisposition for cancer. The location of variants in different regions in BRCA is non-randomly enriched in different types of cancer as shown by the breast cancer cluster region (BCCR), ovarian cancer cluster region (OCCR) and prostate cancer cluster region (PrCCR). Although pathogenic BRCA variation also contributes to pancreatic cancer, no pancreatic cancer cluster region (PcCCR) in BRCA1 or BRCA2 has been identified due to the relatively low i...
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Chian, J. S., Xu, W., Wang, S. M. Tags: Cancer genetics Source Type: research
Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
Conclusion
The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Duenas, N., Klinkhammer, H., Bonifaci, N., Spier, I., Mayr, A., Hassanin, E., Diez-Villanueva, A., Moreno, V., Pineda, M., Maj, C., Capella, G., Aretz, S., Brunet, J. Tags: Cancer genetics Source Type: research
Position statement of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) on APC I1307K and cancer risk
While constitutional pathogenic variants in the APC gene cause familial adenomatous polyposis, APC c.3920T>A; p.Ile1307Lys (I1307K) has been associated with a moderate increased risk of colorectal cancer (CRC), particularly in individuals of Ashkenazi Jewish descent. However, published data include relatively small sample sizes, generating inconclusive results regarding cancer risk, particularly in non-Ashkenazi populations. This has led to different country/continental-specific guidelines regarding genetic testing, clinical management and surveillance recommendations for I1307K. A multidisciplinary international expert...
Source: Journal of Medical Genetics - October 24, 2023 Category: Genetics & Stem Cells Authors: Valle, L., Katz, L. H., Latchford, A., Mur, P., Moreno, V., Frayling, I. M., Heald, B., Capella, G., on behalf of the InSiGHT Council Tags: Open access Position statement Source Type: research
Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C
Conclusion
Through this study, we demonstrated that craniofacial abnormalities are common in patients with POLR3-HLD. This report describes in detail the dysmorphic features of POLR3-HLD associated with biallelic variants in POLR3A, POLR3B and POLR1C. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Mirchi, A., Guay, S.-P., Tran, L. T., Wolf, N. I., Vanderver, A., Brais, B., Sylvain, M., Pohl, D., Rossignol, E., Saito, M., Moutton, S., Gonzalez-Gutierrez-Solana, L., Thiffault, I., Kruer, M. C., Moron, D. G., Kauffman, M., Goizet, C., Sztriha, L., Gla Tags: Open access Neurogenetics Source Type: research
TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype
This report provides key genetic evidence invaluable to establishing the gene-disease relationship for this gene and important insights into the TRAPPC2L phenotype. Regression, seizures and postnatal microcephaly initially described are not constant features. Acute episodes of infection do not contribute to the neurological course. HyperCKaemia is part of the clinical picture. Thus, TRAPPC2L syndrome is mainly characterised by a severe neurodevelopmental disorder and a variable degree of muscle involvement, suggesting that it belongs to the clinical entity of rare congenital muscular dystrophies. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Abaji, M., Mignon-Ravix, C., Gorokhova, S., Cacciagli, P., Mortreux, J., Molinari, F., Chabrol, B., Sigaudy, S., Villard, L., Riccardi, F. Tags: Neurogenetics Source Type: research
Phenotypical differences of C9ORF72 gene-positive and negative amyotrophic lateral sclerosis: a comparative case series
Discussion
Analysis of this ALS clinic cohort at a UK tertiary neurosciences centre adds to the small but growing understanding of the unique clinical features of patients with C9pALS. In the age of precision medicine with expanding opportunities to manage genetic diseases with disease-modifying therapies, clinical identification of such patients is increasingly important as focused therapeutic strategies become available. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: White, L. M., Boardman, J., Lilleker, J., Chaouch, A., Kargwell, H., Ealing, J., Hamdalla, H. Tags: Neurogenetics Source Type: research
Strategic validation of variants of uncertain significance in ECHS1 genetic testing
Conclusions
In summary, this study uncovered new ECHS1 cases based on VUS validation and omics analysis; these analyses are applicable to the functional evaluation of other genes associated with mitochondrial disease. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Kishita, Y., Sugiura, A., Onuki, T., Ebihara, T., Matsuhashi, T., Shimura, M., Fushimi, T., Ichino, N., Nagatakidani, Y., Nishihata, H., Nitta, K. R., Yatsuka, Y., Imai-Okazaki, A., Wu, Y., Osaka, H., Ohtake, A., Murayama, K., Okazaki, Y. Tags: Functional genomics Source Type: research
ARF1-related disorder: phenotypic and molecular spectrum
Conclusion
We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: de Sainte Agathe, J.-M., Pode-Shakked, B., Naudion, S., Michaud, V., Arveiler, B., Fergelot, P., Delmas, J., Keren, B., Poirsier, C., Alkuraya, F. S., Tabarki, B., Bend, E., Davis, K., Bebin, M., Thompson, M. L., Bryant, E. M., Wagner, M., Hannibal, I., L Tags: Open access Developmental defects Source Type: research
Biallelic NPR1 loss of function variants are responsible for neonatal systemic hypertension
Conclusion
We show for the first time that biallelic loss of function of NPR1 is responsible for isolated neonatal-onset systemic hypertension in humans, which represents a new autosomal recessive genetic cause of infantile systemic hypertension or cardiogenic shock. This is consistent with studies reporting early-onset systemic hypertension and sudden death in Npr1-deficient mice. NPR1 gene analysis should be therefore investigated in infants with early-onset systemic hypertension with or without cardiogenic shock of unknown origin. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Capri, Y., Kwon, T., Boyer, O., Bourmance, L., Testa, N., Baudouin, V., Bonnefoy, R., Couderc, A., Meziane, C., Tournier-Lasserve, E., Heidet, L., Melki, J. Tags: Open access Developmental defects Source Type: research
Germline pathogenic SMARCA4 variants in neuroblastoma
Heterozygous germline pathogenic variants (GPVs) in SMARCA4, the gene encoding the ATP-dependent chromatin remodelling protein SMARCA4 (previously known as BRG1), predispose to several rare tumour types, including small cell carcinoma of the ovary, hypercalcaemic type, atypical teratoid and malignant rhabdoid tumour, and uterine sarcoma. The increase in germline testing of SMARCA4 in recent years has revealed putative GPVs affecting SMARCA4 in patients with other cancer types. Here we describe 11 patients with neuroblastoma (NBL), including 4 previously unreported cases, all of whom were found to harbour heterozygous germl...
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Witkowski, L., Nichols, K. E., Jongmans, M., van Engelen, N., de Krijger, R. R., Herrera-Mullar, J., Tytgat, L., Bahrami, A., Mar Fan, H., Davidson, A. L., Robertson, T., Anderson, M., Hasselblatt, M., Plon, S. E., Foulkes, W. D. Tags: Cancer genetics Source Type: research
Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma
Conclusion
We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - September 21, 2023 Category: Genetics & Stem Cells Authors: Corradi, C., Lencioni, G., Gentiluomo, M., Felici, A., Latiano, A., Kiudelis, G., van Eijck, C. H. J., Marta, K., Lawlor, R. T., Tavano, F., Boggi, U., Dijk, F., Cavestro, G. M., Vermeulen, R. C. H., Hackert, T., Petrone, M. C., Uzunoglu, F. G., Archibugi Tags: Cancer genetics Source Type: research
