scholarly journals A de novo ACTB gene pathogenic variant in identical twins with phenotypic variation for hydrops and jejunal atresia

2021 ◽  
Author(s):  
Kristina Sibbin ◽  
Patrick Yap ◽  
Denis Nyaga ◽  
Raoul Heller ◽  
Stephen Evans ◽  
...  
Keyword(s):  
Phenotypic Variation ◽  
De Novo ◽  
Pathogenic Variant ◽  
Identical Twins ◽  
Jejunal Atresia

Beneficial effects of the ketogenic diet on drug-resistant epileptic encephalopathy associated with a de novo NBEA pathogenic variant

2021 ◽  
Vol 23 (5) ◽  
pp. 739-743
Author(s):  
Silvia Schiavoni ◽  
Carlotta Spagnoli ◽  
Susanna Rizzi ◽  
Grazia Gabriella Salerno ◽  
Daniele Frattini ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Pathogenic Variant ◽  
Drug Resistant ◽  
Beneficial Effects

Exome sequencing identified a de novo frameshift pathogenic variant of CTBP1 in an extremely rare case of HADDTS

2021 ◽  
Vol 100 (2) ◽  
Author(s):  
Hossein Jafari Khamirani ◽  
Sina Zoghi ◽  
Ali Saber Sichani ◽  
Mehdi Dianatpour ◽  
Sanaz Mohammadi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Rare Case ◽  
De Novo ◽  
Pathogenic Variant

scholarly journals A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Lulu Yan ◽  
Ru Shen ◽  
Zongfu Cao ◽  
Chunxiao Han ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  
De Novo ◽  
Genetic Disorder ◽  
Neurodevelopmental Disorder ◽  
Three Dimensional ◽  
Missense Variant ◽  
Pathogenic Variant ◽  
Dimensional Structure ◽  
Chinese Family ◽  
Speech Impairment ◽  
Pathogenic Variants

PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome

2021 ◽  
Author(s):  
Carmen Palma ◽  
Pérez Mohand Patricia ◽  
José M. Lezana ◽  
Jaime Cruz ◽  
Juan F. Quesada ◽  
...  
Keyword(s):  
De Novo ◽  
Pathogenic Variant ◽  
Craniofacial Anomalies ◽  
Osteoblast Proliferation ◽  
Terminal Portion ◽  
Transcription Activator ◽  
Palate Development ◽  
Partial Rhombencephalosynapsis ◽  
And Function ◽  
Craniofacial Defects

AbstractMeningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello–Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

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

scholarly journals Cardiofaciocutaneous Syndrome Phenotype in a Case with de novo KRAS Pathogenic Variant

2019 ◽  
Vol 10 (6) ◽  
pp. 344-347
Author(s):  
Aslihan Sanri ◽  
Hakan Gurkan ◽  
Selma Demir
Keyword(s):  
De Novo ◽  
Pathogenic Variant ◽  
Cardiofaciocutaneous Syndrome

Rapidly Progressive Multisutural Craniosynostosis in a Patient With Jackson-Weiss Syndrome and a De Novo FGFR2 Pathogenic Variant

2019 ◽  
Vol 56 (10) ◽  
pp. 1386-1392
Author(s):  
Karel-Bart Celie ◽  
Melissa Yuan ◽  
Christopher Cunniff ◽  
Jarrod Bogue ◽  
Caitlin Hoffman ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Early Treatment ◽  
Clinical Presentation ◽  
De Novo ◽  
Pathogenic Variant ◽  
Medical Complications ◽  
3 Dimensional ◽  
Constitutive Activation ◽  
Pathogenic Variants ◽  
Dimensional Modeling

Little is currently known about the mechanisms by which pathogenic variants of FGFR2 produce changes in the FGFR protein and influence the clinical presentation of affected individuals. We report on a patient with a de novo pathogenic variant of FGFR2 and a phenotype consistent with Jackson-Weiss syndrome who presented with delayed, rapidly progressive multisutural craniosynostosis and associated medical complications. Using 3-dimensional modeling of the FGFR protein, we provide evidence that this variant resulted in abnormal dimerization and constitutive activation of FGFR, leading to the Jackson-Weiss phenotype. Knowledge regarding the correlation between genotype and phenotype of persons with FGFR2-related craniosynostosis has the potential to allow for anticipation of medical complications, institution of early treatment, and improved clinical outcomes.

Identical twins with malrotation and type IV jejunal atresia

1987 ◽  
Vol 22 (11) ◽  
pp. 1015-1016 ◽  
Author(s):  
Laurel Matthews Olson ◽  
L. Suzanne Flom ◽  
Catherine M.P. Kierney ◽  
Dennis W. Shermeta
Keyword(s):  
Identical Twins ◽  
Jejunal Atresia ◽  
Type Iv

scholarly journals Epilepsy and neurobehavioral abnormalities in mice with a KCNB1 pathogenic variant that alters conducting and non-conducting functions of KV2.1

2019 ◽  
Author(s):  
Nicole A. Hawkins ◽  
Sunita N. Misra ◽  
Manuel Jurado ◽  
Nicholas C. Vierra ◽  
Kimberly Nguyen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
De Novo ◽  
Pathogenic Variant ◽  
Repetitive Behaviors ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Delayed Rectifier ◽  
Eeg Abnormalities ◽  
Surface Ecg

AbstractDevelopmental and epileptic encephalopathies (DEE) are a group of severe epilepsies that usually present with intractable seizures, developmental delay and are at a higher risk for premature mortality. Numerous genes have been identified as a monogenic cause of DEE, including KCNB1. The voltage-gated potassium channel KV2.1, encoded by KCNB1, is primarily responsible for delayed rectifier potassium currents that are important regulators of excitability in electrically excitable cells, including neurons and cardiomyocytes. The de novo pathogenic variant KCNB1-p.G379R was identified in an infant with epileptic spasms, atonic, focal and tonic-clonic seizures that were refractory to treatment with standard antiepileptic drugs. Previous work demonstrated deficits in potassium conductance, but did not assess non-conducting functions. To determine if the G379R variant affected clustering at endoplasmic reticulum-plasma membrane junctions KV2.1-G379R was expressed in HEK293T cells. KV2.1-G379R expression did not induce formation of endoplasmic reticulum-plasma membrane junctions, and co-expression of KV2.1-G379R with KV2.1-WT lowered induction of these structures relative to KV2.1-WT alone, suggesting a dominant negative effect. To model this variant in vivo, we introduced Kcnb1G379R into mice using CRISPR/Cas9 genome editing. We characterized neurological and neurobehavioral phenotypes of Kcnb1G379R/+ (Kcnb1R/+) and Kcnb1G379R/G379R (Kcnb1R/R) mice, and screened for cardiac abnormalities. Immunohistochemistry studies on brains from Kcnb1+/+ (WT), Kcnb1R/+ and Kcnb1R/R mice revealed genotype-dependent differences in the levels and subcellular localization of KV2.1, with reduced plasma membrane expression of the KV2.1-G379R protein, consistent with in vitro data. Kcnb1R/+ and Kcnb1R/R mice displayed profound hyperactivity, repetitive behaviors, impulsivity and reduced anxiety. In addition, both Kcnb1R/+ and Kcnb1R/R mice exhibited abnormal interictal EEG abnormalities, including isolated spike and slow waves. Spontaneous seizure events were observed in Kcnb1R/R mice during exposure to novel environments and/or handling, while both Kcnb1R/+ and Kcnb1R/R mutants were more susceptible to induced seizures. Kcnb1R/+ and Kcnb1R/R mice exhibited prolonged rate-corrected QT interval on surface ECG recording. Overall, the Kcnb1G379R mice recapitulate many features observed in individuals with DEE due to pathogenic variants in KCNB1. This new mouse model of KCNB1 associated DEE will be valuable for improving the understanding of the underlying pathophysiology and will provide a valuable tool for the development of therapies to treat this pharmacoresistant DEE.

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