scholarly journals A Review of the Genomic Analysis of Children Presenting with Developmental Delay/Intellectual Disability and Associated Dysmorphic Features

Cureus ◽  
2019 ◽  
Author(s):  
Ramiah R Vickers ◽  
Jane S Gibson
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genomic Analysis ◽  
Dysmorphic Features

scholarly journals Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features

Brain ◽  
2017 ◽  
Vol 140 (11) ◽  
pp. 2879-2894 ◽  
Author(s):  
Cristina Elena Niturad ◽  
Dorit Lev ◽  
Vera M Kalscheuer ◽  
Agnieszka Charzewska ◽  
Julian Schubert ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Gabaa Receptor ◽  
Xenopus Laevis Oocytes ◽  
Incomplete Penetrance ◽  
Single Mutation ◽  
Loss Of Function ◽  
Missense Variants ◽  
Dysmorphic Features ◽  
Α3 Subunit

Abstract Genetic epilepsies are caused by mutations in a range of different genes, many of them encoding ion channels, receptors or transporters. While the number of detected variants and genes increased dramatically in the recent years, pleiotropic effects have also been recognized, revealing that clinical syndromes with various degrees of severity arise from a single gene, a single mutation, or from different mutations showing similar functional defects. Accordingly, several genes coding for GABAA receptor subunits have been linked to a spectrum of benign to severe epileptic disorders and it was shown that a loss of function presents the major correlated pathomechanism. Here, we identified six variants in GABRA3 encoding the α3-subunit of the GABAA receptor. This gene is located on chromosome Xq28 and has not been previously associated with human disease. Five missense variants and one microduplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies. Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype. X-chromosome inactivation studies could not explain the phenotypic variability in females. Three detected missense variants are localized in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the α3-subunit. Functional studies in Xenopus laevis oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype. The microduplication disrupted GABRA3 expression in fibroblasts of the affected patient. In summary, our results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern. 10.1093/brain/awx236_video1 awx236media1 5636589232001

scholarly journals Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features

Neurogenetics ◽  
2016 ◽  
Vol 17 (3) ◽  
pp. 159-164 ◽  
Author(s):  
Hallie Steinfeld ◽  
Megan T. Cho ◽  
Kyle Retterer ◽  
Rick Person ◽  
G. Bradley Schaefer ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Dysmorphic Features

scholarly journals De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features

2016 ◽  
Vol 2 (6) ◽  
pp. a001172 ◽  
Author(s):  
Emily Webster ◽  
Megan T. Cho ◽  
Nora Alexander ◽  
Sonal Desai ◽  
Sakkubai Naidu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Dysmorphic Features

Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features

2020 ◽  
Vol 63 (4) ◽  
pp. 103804 ◽  
Author(s):  
Tokiko Fukuda ◽  
Takuya Hiraide ◽  
Kaori Yamoto ◽  
Mitsuko Nakashima ◽  
Tomoko Kawai ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Global Developmental Delay ◽  
Dysmorphic Features

scholarly journals Shukla-Vernon Syndrome: A Second Family with a Novel Variant in the BCORL1 Gene

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 452
Author(s):  
Babylakshmi Muthusamy ◽  
Anikha Bellad ◽  
Satish Chandra Girimaji ◽  
Akhilesh Pandey
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Protein Complexes ◽  
Neurodevelopmental Disorder ◽  
Missense Variant ◽  
Global Developmental Delay ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Behavioral Abnormalities ◽  
Novel Variant

Shukla-Vernon syndrome (SHUVER) is an extremely rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral anomalies, and dysmorphic features. Pathogenic variants in the BCORL1 gene have been identified as the molecular cause for this disorder. The BCORL1 gene encodes for BCL-6 corepressor-like protein 1, a transcriptional corepressor that is an integral component of protein complexes involved in transcription repression. In this study, we report an Indian family with two male siblings with features of Shukla-Vernon syndrome. The patients exhibited global developmental delay, intellectual disability, kyphosis, seizures, and dysmorphic features including bushy prominent eyebrows with synophrys, sharp beaked prominent nose, protuberant lower jaw, squint, and hypoplastic ears with fused ear lobes. No behavioral abnormalities were observed. Whole exome sequencing revealed a novel potentially pathogenic arginine to cysteine substitution (p.Arg1265Cys) in the BCORL1 protein. This is the second report of Shukla-Vernon syndrome with a novel missense variant in the BCORL1 gene. Our study confirms and expands the phenotypes and genotypes described previously for this syndrome and should aid in diagnosis and genetic counselling of patients and their families.

scholarly journals Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

2020 ◽  
Vol 8 ◽  
pp. 232470962095777 ◽  
Author(s):  
Maria Elena Romero-Ibarguengoitia ◽  
Consuelo Cantú-Reyna ◽  
Dalia Gutierrez-González ◽  
Héctor Cruz-Camino ◽  
Arnulfo González-Cantú ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Variants ◽  
Therapeutic Approaches ◽  
Multisystem Disorder ◽  
Related Disorder ◽  
Dysmorphic Features ◽  
The Third ◽  
The Central Nervous System ◽  
Mexican Patient

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.

TBL1XR1 associated intellectual disability, a new missense variant with dysmorphic features plus autism: Expanding the phenotypic spectrum

2021 ◽  
Author(s):  
Ignacio Arroyo Carrera ◽  
Miguel Fernández‐Burriel ◽  
Pablo Lapunzina ◽  
Jair Antonio Tenorio ◽  
Verónica Deyanira García Navas ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Missense Variant ◽  
Dysmorphic Features ◽  
Phenotypic Spectrum
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