Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features

2018 ◽  
Vol 176 (12) ◽  
pp. 2548-2553 ◽  
Author(s):  
Caleb P. Bupp ◽  
Chad R. Schultz ◽  
Katie L. Uhl ◽  
Surender Rajasekaran ◽  
André S. Bachmann
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Pathogenic Variant ◽  
Dysmorphic Features

Developmental delay and dysmorphic features in a girl with a de novo 5.4 Mb deletion of 13q12.11‐q12.13

2019 ◽  
Vol 60 (2) ◽  
pp. 73-74
Author(s):  
Makiko Tominaga ◽  
Toshiyuki Saito ◽  
Mitsuo Masuno ◽  
You Umeda ◽  
Kenji Kurosawa
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Dysmorphic Features

De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay

2017 ◽  
Vol 173 (10) ◽  
pp. 2725-2730 ◽  
Author(s):  
Resham Ejaz ◽  
Anath C. Lionel ◽  
Susan Blaser ◽  
Susan Walker ◽  
Stephen W. Scherer ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Pathogenic Variant ◽  
Arthrogryposis Multiplex Congenita ◽  
Brain Abnormalities

De novo variants in SIAH1, encoding an E3 ubiquitin ligase, are associated with developmental delay, hypotonia and dysmorphic features

2020 ◽  
pp. jmedgenet-2019-106335
Author(s):  
Julien Buratti ◽  
Lei Ji ◽  
Boris Keren ◽  
Youngha Lee ◽  
Stephanie Booke ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Developmental Delay ◽  
Ubiquitin Ligase ◽  
De Novo ◽  
E3 Ubiquitin Ligase ◽  
Hek293 Cells ◽  
Luciferase Reporter ◽  
Mendelian Disease ◽  
Dysmorphic Features ◽  
Stimulatory Activity

BackgroundUbiquitination has a central role in numerous biological processes, including cell development, stress responses and ageing. Perturbed ubiquitination has been implicated in human diseases ranging from cancer to neurodegenerative diseases. SIAH1 encodes a RING-type E3 ubiquitin ligase involved in protein ubiquitination. Among numerous other roles, SIAH1 regulates metabotropic glutamate receptor signalling and affects neural cell fate. Moreover, SIAH1 positively regulates Wnt signalling through ubiquitin-mediated degradation of Axin and accumulation of β-catenin.MethodsTrio exome sequencing followed by Sanger validation was undertaken in five individuals with syndromic developmental delay. Three-dimensional structural modelling was used to predict pathogenicity of affected residues. Wnt stimulatory activity was measured by luciferase reporter assays and Axin degradation assays in HEK293 cells transfected with wild-type and mutant SIAH1 expression plasmids.ResultsWe report five unrelated individuals with shared features of developmental delay, infantile hypotonia, dysmorphic features and laryngomalacia, in whom exome sequencing identified de novo monoallelic variants in SIAH1. In silico protein modelling suggested alteration of conserved functional sites. In vitro experiments demonstrated loss of Wnt stimulatory activity with the SIAH1 mutants, suggesting variant pathogenicity.ConclusionOur results lend support to SIAH1 as a candidate Mendelian disease gene for a recognisable syndrome, further strengthening the connection between SIAH1 and neurodevelopmental disorders. Furthermore, the results suggest that dysregulation of the Wnt/β-catenin pathway may be involved in the pathogenesis.

scholarly journals Multiple Coronary Artery Microfistulas in a Girl with Kleefstra Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Euthymia Vargiami ◽  
Athina Ververi ◽  
Hamda Al-Mutawa ◽  
Georgia Gioula ◽  
Spyridon Gerou ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Developmental Delay ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
De Novo ◽  
Heart Defects ◽  
Dysmorphic Features ◽  
Kleefstra Syndrome

Kleefstra syndrome is characterized by hypotonia, developmental delay, dysmorphic features, congenital heart defects, and so forth. It is caused by 9q34.3 microdeletions orEHMT1mutations. Herein a 20-month-old girl with Kleefstra syndrome, due to a de novo subterminal deletion, is described. She exhibits a rare and complex cardiopathy, encompassing multiple coronary artery microfistulas, VSD/ASD, and PFO.

A de novo 17q21.2 duplication in a boy with developmental delay and dysmorphic features

2013 ◽  
Vol 56 (4) ◽  
pp. 226-228 ◽  
Author(s):  
Céline Poirsier-Violle ◽  
Azzedine Abourra ◽  
Clarisse Baumann ◽  
Laurence Perrin ◽  
Yline Capri ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Dysmorphic Features

scholarly journals Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features

2015 ◽  
Author(s):  
Jessica X. Chong ◽  
Joon-Ho Yu ◽  
Peter Lorentzen ◽  
Karen M. Park ◽  
Seema M. Jamal ◽  
...  
Keyword(s):  
Social Networking ◽  
Developmental Delay ◽  
De Novo ◽  
Gene Discovery ◽  
Pathogenic Variant ◽  
Facial Features ◽  
Variants Of Unknown Significance ◽  
Mendelian Gene ◽  
Unknown Significance ◽  
Share Data

ABSTRACTPurpose:The pace of Mendelian gene discovery is slowed by the “n-of-1 problem” – the difficulty of establishing causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier but is often impeded by lack of a convenient or widely-available way to share data on candidate variants / genes among families, clinicians and researchers.Methods:Social networking among families, clinicians and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes.Results:De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features.Conclusion:Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with non-specific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP). Design and development of a web-based tool, MyGene2, that enables families, clinicians and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP is underway.

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