Evaluating the Role of MAST1 as an Intellectual Disability Disease Gene: Identification of a Novel De Novo Variant in a Patient with Developmental Disabilities

2019 ◽  
Vol 70 (3) ◽  
pp. 320-327 ◽  
Author(s):  
Afif Ben-Mahmoud ◽  
Aisha M. Al-Shamsi ◽  
Bassam R. Ali ◽  
Lihadh Al-Gazali
Keyword(s):  
Intellectual Disability ◽  
Developmental Disabilities ◽  
Disease Gene ◽  
De Novo ◽  
Gene Identification ◽  
De Novo Variant

scholarly journals A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

scholarly journals A de novo variant in the X‐linked gene CNKSR2 is associated with seizures and mild intellectual disability in a female patient

2019 ◽  
Vol 7 (10) ◽  
Author(s):  
Daniel L. Polla ◽  
Harriet R. Saunders ◽  
Bert B. A. Vries ◽  
Hans Bokhoven ◽  
Arjan P. M. Brouwer
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
De Novo ◽  
Mild Intellectual Disability ◽  
Linked Gene ◽  
De Novo Variant

scholarly journals Functional analysis of a de novo variant in the neurodevelopment and generalized epilepsy disease gene NBEA

2021 ◽  
Author(s):  
Thomas Boulin ◽  
Omar Itani ◽  
Sonia El Mouridi ◽  
Alice Leclercq-Blondel ◽  
Ellen Macnamara ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Disease Gene ◽  
De Novo ◽  
Generalized Epilepsy ◽  
De Novo Variant

scholarly journals De novo Variants in Neurodevelopmental Disorders with Epilepsy

2017 ◽  
Author(s):  
Henrike O. Heyne ◽  
Tarjinder Singh ◽  
Hannah Stamberger ◽  
Rami Abou Jamra ◽  
Hande Caglayan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Testing ◽  
Neurodevelopmental Disorders ◽  
Disease Gene ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Disease Association ◽  
Joint Analysis ◽  
Limited Evidence ◽  
Significant Excess

AbstractEpilepsy is a frequent feature of neurodevelopmental disorders (NDD) but little is known about genetic differences between NDD with and without epilepsy. We analyzed de novo variants (DNV) in 6753 parent-offspring trios ascertained for different NDD. In the subset of 1942 individuals with NDD with epilepsy, we identified 33 genes with a significant excess of DNV, of which SNAP25 and GABRB2 had previously only limited evidence for disease association. Joint analysis of all individuals with NDD also implicated CACNA1E as a novel disease gene. Comparing NDD with and without epilepsy, we found missense DNV, DNV in specific genes, age of recruitment and severity of intellectual disability to be associated with epilepsy. We further demonstrate to what extent our results impact current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDD with epilepsy.

scholarly journals Novel clinical and genetic insight into CXorf56-associated intellectual disability

2019 ◽  
Vol 28 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Maria Eugenia Rocha ◽  
Tainá Regina Damaceno Silveira ◽  
Erina Sasaki ◽  
Daíse Moreno Sás ◽  
Charles Marques Lourenço ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Causative Role ◽  
Loss Of Function ◽  
Abnormal Gait ◽  
Genomic Approach ◽  
Neurological Features ◽  
Male Patients ◽  
Molecular Anatomy

AbstractIntellectual disability (ID) is one of most frequent reasons for genetic consultation. The complex molecular anatomy of ID ranges from complete chromosomal imbalances to single nucleotide variant changes occurring de novo, with thousands of genes identified. This extreme genetic heterogeneity challenges the molecular diagnosis, which mostly requires a genomic approach. CXorf56 is largely uncharacterized and was recently proposed as a candidate ID gene based on findings in a single Dutch family. Here, we describe nine cases (six males and three females) from three unrelated families. Exome sequencing and combined database analyses, identified family-specific CXorf56 variants (NM_022101.3:c.498_503del, p.(Glu167_Glu168del) and c.303_304delCTinsACCC, p.(Phe101Leufs*20)) that segregated with the ID phenotype. These variants are presumably leading to loss-of-function, which is the proposed disease mechanism. Clinically, CXorf56-related disease is a slowly progressive neurological disorder. The phenotype is more severe in hemizygote males, but might also manifests in heterozygote females, which showed skewed X-inactivation patterns in blood. Male patients might present previously unreported neurological features such as epilepsy, abnormal gait, tremor, and clonus, which extends the clinical spectrum of the disorder. In conclusion, we confirm the causative role of variants in CXorf56 for an X-linked form of intellectual disability with additional neurological features. The gene should be considered for molecular diagnostics of patients with ID, specifically when family history is suggestive of X-linked inheritance. Further work is needed to understand the role of this gene in neurodevelopment and intellectual disability.

scholarly journals De Novo 1q21.3q22 Duplication Revaluation in a “Cold” Complex Neuropsychiatric Case with Syndromic Intellectual Disability

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 511
Author(s):  
Roberta Milone ◽  
Roberta Scalise ◽  
Rosa Pasquariello ◽  
Stefano Berloffa ◽  
Ivana Ricca ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Spastic Paraparesis ◽  
Genetic Diagnosis ◽  
Pathogenic Role ◽  
Moderate Intellectual Disability ◽  
Contiguous Gene ◽  
Generation Sequencing ◽  
Duplication Syndrome

Syndromic intellectual disability often obtains a genetic diagnosis due to the combination of first and next generation sequencing techniques, although their interpretation may require revaluation over the years. Here we report on a composite neuropsychiatric case whose phenotype includes moderate intellectual disability, spastic paraparesis, movement disorder, and bipolar disorder, harboring a 1.802 Mb de novo 1q21.3q22 duplication. The role of this duplication has been reconsidered in the light of negativity of many other genetic exams, and of the possible pathogenic role of many genes included in this duplication, potentially configuring a contiguous gene-duplication syndrome.

scholarly journals The int22h1/int22h2-Mediated Xq28 Duplication Syndrome: An Intersection between Neurodevelopment, Immunology, and Cancer

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 860
Author(s):  
Rami A. Ballout ◽  
Ayman W. El-Hattab
Keyword(s):  
Intellectual Disability ◽  
X Chromosome ◽  
Potential Role ◽  
Pediatric Patients ◽  
De Novo ◽  
Facial Features ◽  
Immunological Responses ◽  
Xq28 Duplication ◽  
Duplication Syndrome

The int22h1/int22h2-mediated Xq28 duplication syndrome is a rare X-linked intellectual disability syndrome (XLIDS) arising from a duplication of the segment between intron 22 homologous regions 1 and 2, on the q28 subregion of the X chromosome. The main clinical features of the syndrome include intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. Due to the X-linked nature of the syndrome, affected males exhibit more severe phenotypes compared with heterozygous females. A unique distinguishing feature of the syndrome across the sexes, however, is a peculiar combination of recurrent sinopulmonary infections and atopy exclusively seen in a subset of affected males. In addition to the ‘typical’ 0.5 Mb duplication detected in most cases reported to date with the syndrome, a shortened centromeric version, and another 0.2 Mb telomerically shifted one, have been recently identified, with most detected duplications being maternally inherited, except for three recent cases found to have de novo duplications. Interestingly, a recently reported case of an affected male suggests a possible association of the syndrome with multiple malignancies, an observation that has been recently replicated in two pediatric patients. As a result, a better understanding of the pathogenesis of int22h1/int22h2-mediated Xq28 duplication syndrome may grant us a better understanding of the sex-specific differences in immunological responses, as well as the potential role of the genes involved by the duplication, in oncogenesis.

Examining the Role of Language in Play Among Children With and Without Developmental Disabilities

2020 ◽  
Vol 51 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Elizabeth J. Short ◽  
Rachael Cooper Schindler ◽  
Rita Obeid ◽  
Maia M. Noeder ◽  
Laura E. Hlavaty ◽  
...  
Keyword(s):  
Developmental Disabilities ◽  
Autism Spectrum ◽  
Free Play ◽  
Group Differences ◽  
Typically Developing ◽  
Play Skills ◽  
Critical Aspect ◽  
Hyperactivity Disorder ◽  
Better Than

Purpose Play is a critical aspect of children's development, and researchers have long argued that symbolic deficits in play may be diagnostic of developmental disabilities. This study examined whether deficits in play emerge as a function of developmental disabilities and whether our perceptions of play are colored by differences in language and behavioral presentations. Method Ninety-three children participated in this study (typically developing [TD]; n = 23, developmental language disorders [DLD]; n = 24, attention-deficit/hyperactivity disorder [ADHD]; n = 26, and autism spectrum disorder [ASD]; n = 20). Children were videotaped engaging in free-play. Children's symbolic play (imagination, organization, elaboration, and comfort) was scored under conditions of both audible language and no audible language to assess diagnostic group differences in play and whether audible language impacted raters' perception of play. Results Significant differences in play were evident across diagnostic groups. The presence of language did not alter play ratings for the TD group, but differences were found among the other diagnostic groups. When language was audible, children with DLD and ASD (but not ADHD) were scored poorly on play compared to their TD peers. When language was not audible, children with DLD were perceived to play better than when language was audible. Conversely, children with ADHD showed organizational deficits when language was not available to support their play. Finally, children with ASD demonstrated poor play performance regardless of whether language was audible or not. Conclusions Language affects our understanding of play skills in some young children. Parents, researchers, and clinicians must be careful not to underestimate or overestimate play based on language presentation. Differential skills in language have the potential to unduly influence our perceptions of play for children with developmental disabilities.

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