FSIP2 plays a role in the acrosome development during spermiogenesis
Conclusion
Our findings unveil that FSIP2 might involve in sperm acrosome development, and consequently, its mutations might contribute to globozoospermia or acrosomal aplasia. We meanwhile first uncover the potential molecular mechanism of FSIP2 regulating acrosome biogenesis. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Zheng, R., Wang, Y., Li, Y., Guo, J., Wen, Y., Jiang, C., Yang, Y., Shen, Y. Tags: Genotype-phenotype correlations Source Type: research
Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project
Conclusion
This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Wang, H., Xiao, F., Qian, Y., Wu, B., Dong, X., Lu, Y., Cheng, G., Wang, L., Yan, K., Yang, L., Chen, L., Kang, W., Li, L., Pan, X., Wei, Q., Zhuang, D., Chen, D., Yin, Z., Yang, L., Ni, Q., Liu, R., Li, G., Zhang, P., Li, X., Peng, X., Wang, Y., Chen, H. Tags: Population genetics Source Type: research
Decision-making and regret in patients with germline CDH1 variants undergoing prophylactic total gastrectomy
Conclusion
The decision to undergo PTG is influenced by family cancer history and surveillance endoscopy results. Regret is associated with surgical complications and pathological absence of cancer. Individual cancer-risk assessment is necessary to improve pre-operative counselling and inform the decision-making process.
Trial registration number
NCT03030404. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Gamble, L. A., Grant, R. R. C., Samaranayake, S. G., Fasaye, G.-A., Koh, C., Korman, L., Asif, B., Heller, T., Hernandez, J. M., Blakely, A. M., Davis, J. L. Tags: Cancer genetics Source Type: research
A homozygous variant in CHMP3 is associated with complex hereditary spastic paraplegia
Conclusions
Reduced level of CHMP3 is associated with complex spastic paraplegia phenotype, through aberrant autophagy mechanisms. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Cohen-Barak, E., Danial-Farran, N., Chervinsky, E., Alimi-Kasem, O., Zagairy, F., Livneh, I., Mawassi, B., Hreish, M., Khayat, M., Lossos, A., Meiner, V., Ehilevitch, N., Weiss, K., Shalev, S. Tags: Neurogenetics Source Type: research
Gain-of-function p.F28S variant in RAC3 disrupts neuronal differentiation, migration and axonogenesis during cortical development, leading to neurodevelopmental disorder
Conclusion
Our results indicate that RAC3 is critical for brain development and the p.F28S variant causes morphological and functional defects in cortical neurons, likely due to the hyperactivation of PAK1. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Nishikawa, M., Scala, M., Umair, M., Ito, H., Waqas, A., Striano, P., Zara, F., Costain, G., Capra, V., Nagata, K.-i. Tags: Neurogenetics Source Type: research
Histones: coming of age in Mendelian genetic disorders
Histones hold significant interest in development and genetic disorders due to their critical roles in chromatin dynamics, influencing gene expression and genome integrity. These roles are linked to alterations of post-translational marks, which are generally concentrated in the histone tails. The machinery modifying or interpreting these marks, known as chromatin writers, erasers or readers, have been associated with many Mendelian disorders; however, it has been only recently that the histone proteins themselves have been directly implicated in Mendelian conditions. High throughput sequencing has recently identified muta...
Source: Journal of Medical Genetics - February 23, 2023 Category: Genetics & Stem Cells Authors: Knapp, K., Naik, N., Ray, S., van Haaften, G., Bicknell, L. S. Tags: Review Source Type: research
Clinical, radiological and molecular studies in 24 individuals with Dyggve-Melchior-Clausen dysplasia and Smith-McCort dysplasia from India
Conclusion
This large cohort from India contributes to the increasing knowledge of clinical and molecular findings in these rare ‘Golgipathies’. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Varshney, K., Narayanachar, S. G., Girisha, K. M., Bhavani, G. S., Narayanan, D., Phadke, S., Nampoothiri, S., Udupi, G. A., Raghupathy, P., Nair, M., Geetha, T. S., Bhat, M. Tags: Phenotypes Source Type: research
GLRA2 gene mutations cause high myopia in humans and mice
Conclusion
GLRA2 was identified as a novel HM-causing gene. Its variants would cause HM through altered visual experience by impairing photoperception and visual transmission. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Tian, Q., Tong, P., Chen, G., Deng, M., Cai, T., Tian, R., Zhang, Z., Xia, K., Hu, Z. Tags: Open access Novel disease loci Source Type: research
Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B
Conclusion
These findings expand our understanding of the clinical and imaging features of the ‘NMDARopathy’ spectrum and contribute to our understanding of the likely underlying pathogenic mechanisms leading to MCD in these patients. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Brock, S., Laquerriere, A., Marguet, F., Myers, S. J., Hongjie, Y., Baralle, D., Vanderhasselt, T., Stouffs, K., Keymolen, K., Kim, S., Allen, J., Shaulsky, G., Chelly, J., Marcorelle, P., Aziza, J., Villard, L., Sacaze, E., de Wit, M. C. Y., Wilke, M., M Tags: Genotype-phenotype correlations Source Type: research
Novel truncating variants in CTNNB1 cause familial exudative vitreoretinopathy
Conclusion
Our findings reinforced the current pathogenesis of Norrin/β-catenin for FEVR and expanded the causative variant spectrum of CTNNB1 for the prenatal diagnosis and genetic counselling of FEVR. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: He, Y., Yang, M., Zhao, R., Peng, L., Dai, E., Huang, L., Zhao, P., Li, S., Yang, Z. Tags: Genotype-phenotype correlations Source Type: research
Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants
Conclusion
We confirm that (1) molecular diagnostic yield increases when multiple tissues are tested and by enriching NGS panels with genes of overlapping ‘vascular’ phenotypes; (2) strongly activating PIK3CA variants are found in affected tissue, rarely in blood: conversely, weakly activating mutations more common in blood; (3) weakly activating variants correlate with CNS involvement, strong variants are more common in cases without; (4) patients with vascular malformations overlapping those of PROS can harbour variants in genes other than PIK3CA. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Mussa, A., Leoni, C., Iacoviello, M., Carli, D., Ranieri, C., Pantaleo, A., Buonuomo, P. S., Bagnulo, R., Ferrero, G. B., Bartuli, A., Melis, D., Maitz, S., Loconte, D. C., Turchiano, A., Piglionica, M., De Luisi, A., Susca, F. C., Bukvic, N., Forleo, C., Tags: Genotype-phenotype correlations Source Type: research
Biallelic mutations in ARMC12 cause asthenozoospermia and multiple midpiece defects in humans and mice
Conclusion
Our findings prove for the first time that defects in ARMC12 cause asthenozoospermia and multiple midpiece defects in humans. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Liu, W., Wei, X., Liu, X., Chen, G., Zhang, X., Liang, X., Isachenko, V., Sha, Y., Wang, Y. Tags: Gametes Source Type: research
Biallelic CFAP61 variants cause male infertility in humans and mice with severe oligoasthenoteratozoospermia
Conclusions
Our findings indicate that CFAP61 is essential for spermatogenesis and that biallelic CFAP61 variants lead to male infertility in humans and mice with OAT. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Hu, T., Meng, L., Tan, C., Luo, C., He, W.-B., Tu, C., Zhang, H., Du, J., Nie, H., Lu, G.-X., Lin, G., Tan, Y.-Q. Tags: Gametes Source Type: research
Homozygous variants in AKAP3 induce asthenoteratozoospermia and male infertility
Conclusions
Our study revealed AKAP3 as a novel gene involved in human asthenoteratozoospermia. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Liu, C., Shen, Y., Tang, S., Wang, J., Zhou, Y., Tian, S., Wu, H., Cong, J., He, X., Jin, L., Cao, Y., Yang, Y., Zhang, F. Tags: Gametes Source Type: research
A 132 bp deletion affecting the KCNQ1OT1 gene associated with Silver-Russell syndrome clinical phenotype
Conclusion
Only six cases have been reported with deletions involving exclusively IC2, one being identical to our proband’s 132 bp deletion. Our study, which is based on more extensive segregation data than the previous 132 bp deletion report, confirms the association of this deletion with growth restriction when paternally inherited. Remarkably, even though our patient has the same deletion, he has more pronounced phenotypic features; our findings thus suggest that some degree of clinical variability may be associated with this loss. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 24, 2023 Category: Genetics & Stem Cells Authors: Gaudet, M. V., Allain, E. P., Gallant, L. M., Arts, H. H., Ben Amor, M. Tags: Open access Epigenetics Source Type: research
