104 research outputs found
Malformations veineuses liées à des mutations du gène TEK : illustration d’un continuum clinique et génétique à partir d’un cas de syndrome de Bean
No full textAutosomal recessive IFT57 hypomorphic mutation cause ciliary transport defect in unclassified oral-facial-digital syndrome with short stature and brachymesophalangia
No full textThe 13 subtypes of oral-facial-digital syndrome (OFDS) belong to the heterogeneous group of ciliopathies. Disease-causing genes encode for centrosomal proteins, components of the transition zone or proteins implicated in ciliary signaling. A unique consanguineous family presenting with an unclassified OFDS with skeletal dysplasia and brachymesophalangia was explored. Homozygosity mapping and exome sequencing led to the identification of a homozygous mutation in IFT57, which encodes a protein implicated in ciliary transport. The mutation caused splicing anomalies with reduced expression of the wild-type transcript and protein. Both anterograde ciliary transport and sonic hedgehog signaling were significantly decreased in subjects' fibroblasts compared with controls. Sanger sequencing of IFT57 in 13 OFDS subjects and 12 subjects with Ellis-Van Creveld syndrome was negative. This report identifies the implication of IFT57 in human pathology and highlights the first description of a ciliary transport defect in OFDS, extending the genetic heterogeneity of this subgroup of ciliopathies
Author Correction: Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome [Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0498-4, published online 30 September 2019]
No full textIndexation en cours. In the version of this article initially published, support from the Wellcome Trust and NIHR to author Veronica A. Kinsler was not included in the Acknowledgements. The error has been corrected in the HTML and PDF versions of the article.International audienceAn amendment to this paper has been published and can be accessed via a link at the top of the paper
Correction: A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis (European Journal of Human Genetics, (2021), 29, 9, (1359-1368), 10.1038/s41431-021-00900-2)
No full textIn the original publication of the article, consortium author lists were missing in the article. The details are as below
Whole-exome sequencing identifies the first French MODY 6 family with a new mutation in the NEUROD1 gene
No full textInternational audienc
Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes
No full textHere the authors characterize structural variations (SVs) in a cohort of individuals with complex genomic rearrangements, identifying breakpoints by employing short- and long-read genome sequencing and investigate their impact on gene expression and the three-dimensional chromatin architecture. They find breakpoints are enriched in inactive regions and can result in chromatin domain fusions.Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements
Correction: A <em>MT-TL1</em> variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis
No full text\ua9 The Author(s), under exclusive licence to European Society of Human Genetics 2021In the original publication of the article, consortium author lists were missing in the article. The details are as below
Author Correction: Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome
No full textPublished Erratum: Correction to: Nature Genetics 51: 1438–1441 https://doi.org/10.1038/s41588-019-0498-4, published online 30 September 2019.In the version of this article initially published, authors Bénédicte Demeer and Bernard Devauchelle were missing the affiliation EA CHIMERE–7516, Université Picardie Jules Verne, Amiens, France. The error has been corrected in the HTML and PDF versions of the article.An amendment to this paper has been published and can be accessed via a link at the top of the paper
Correction: Solving unsolved rare neurological diseases—a Solve-RD viewpoint (European Journal of Human Genetics, (2021), 29, 9, (1332-1336), 10.1038/s41431-021-00901-1)
No full textIn the original publication of the article, consortium author lists were missing in the article. The details are given below
TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation
No full textIF 2.264International audiencePierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in eight patients by whole‐exome sequencing. A dominant‐negative effect of this mutation is strongly suspected, since patients with TBL1XR1 deletion and other variants predicting loss of function do not share the same phenotype. We report two patients with typical Pierpont‐like syndrome features. Exome sequencing allowed identifying a de novo heterozygous missense TBL1XR1 variant in both patients, different from those already reported: p.Cys325Tyr and p.Tyr446His. The localization of these mutations and clinical features of Pierpont‐like syndrome suggest that their functional consequences are comparable with the recurrent mutation previously described, and provided additional data to understand molecular mechanisms of TBL1XR1 anomalies
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