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.

scholarly journals Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability

2018 ◽  
Vol 176 (4) ◽  
pp. 973-979 ◽  
Author(s):  
Wenmiao Zhu ◽  
Jianli Li ◽  
Stella Chen ◽  
Jinglan Zhang ◽  
Francesco Vetrini ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Novel Mutations ◽  
Moderate Intellectual Disability

scholarly journals Obstetric complications and mild to moderate intellectual disability

2009 ◽  
Vol 194 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Jessika E. Sussmann ◽  
Andrew M. McIntosh ◽  
Stephen M. Lawrie ◽  
Eve C. Johnstone
Keyword(s):  
Intellectual Disability ◽  
Genetic Factors ◽  
Special Care ◽  
Foetal Distress ◽  
Neonatal Complications ◽  
Moderate Intellectual Disability ◽  
Special Care Baby Unit ◽  
Increased Risk ◽  
Pregnancy And Delivery

BackgroundMild to moderate intellectual disability affects 2.5% of the general population and is associated with an increased risk of several psychiatric disorders. Most cases are of unknown aetiology although genetic factors have an important role.AimsTo investigate the role of obstetric and neonatal complications in the aetiology of mild to moderate intellectual disability.MethodObstetric and neonatal complications recorded at the time of pregnancy and delivery were compared between participants with mild to moderate intellectual disability, age-matched siblings and unrelated controls using logistic regression.ResultsAdmission to a special care baby unit and not being breastfed on discharge were more common in people with mild to moderate intellectual disability. Not being breastfed on discharge was also more common in those with intellectual disability than unaffected siblings. Foetal distress was more common among controls than among those with mild to moderate intellectual disability.ConclusionsAdmission to a special care baby unit and not being breastfed on discharge may be related to the aetiology of intellectual disability, although the direction of this association is unclear.

scholarly journals A De Novo Xp11.23 Duplication in a Girl with a Severe Phenotype: Expanding the Clinical Spectrum

2017 ◽  
Vol 07 (02) ◽  
pp. 074-077
Author(s):  
Pinar Arican ◽  
Dilek Cavusoglu ◽  
Pinar Gencpinar ◽  
Berk Ozyilmaz ◽  
Taha Ozdemir ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Synovial Sarcoma ◽  
De Novo ◽  
Clinical Spectrum ◽  
Global Developmental Delay ◽  
Speech Delay ◽  
Severe Phenotype ◽  
First Case ◽  
Duplication Syndrome

AbstractThe Xp11.22–p11.23 duplication syndrome was described in 2009 by Giorda et al and is characterized by intellectual disability, speech delay, and electroencephalography anomalies. We report a case of a 23-month-old girl who presented with epilepsy and global developmental delay and who had a small duplication at Xp11.23. The case we present here is the first case showing the clinical features of Xp11.22–p11.23 duplication syndrome only involving synovial sarcoma, X breakpoint (SSX) genes: SSX1, SSX3, SSX4, and SSX9. This case report contributes to an expanding clinical spectrum of Xp11.22–p11.23 duplication syndrome.

scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

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 A novel de novo hemizygous ARHGEF9 mutation associated with severe intellectual disability and epilepsy: a case report

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110583
Author(s):  
Tong Qiu ◽  
Qian Dai ◽  
Qiu Wang
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
De Novo ◽  
Clinical Symptoms ◽  
Genetic Diagnosis ◽  
Epileptic Seizures ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Severe Intellectual Disability

ARHGEF9 encodes collybistin, a brain-specific guanosine diphosphate-guanosine-5′-triphosphate exchange factor that plays an important role in clustering of gephyrin and γ-aminobutyric acid type A receptors in the postsynaptic membrane. Overwhelming evidence suggests that defects in this protein can cause X-linked intellectual disability, which comprises a series of clinical phenotypes, including autism spectrum disorder, behavior disorder, intellectual disability, and febrile seizures. Here, we report a boy with clinical symptoms of severe intellectual disability, epilepsy, and developmental delay and regression. Trio exome sequencing ( trio-clinical exome sequencing) identified a novel hemizygous deletion, c.656_c.669delACTTCTTTGAGGCC (p. His219Leu fs*9), in exon 5 of ARHGEF9. This variant was not reported in either the Genome Aggregation Database or our database of 309 patients with neurodevelopmental disorders. Oxcarbazepine and levetiracetam reduced the frequency of the patient’s epileptic seizures to a certain extent, but psychomotor developmental delay and developmental regression became more obvious with age. This case study seeks to report a de novo loss-of-function mutation of ARHGEF9, aiming to emphasize the genetic diagnosis of X-linked intellectual disability and further improve knowledge of the ethnic distribution of ARHGEF9 mutations.

Employability skills and quality of life among employees with mild and moderate intellectual disability who attend occupation centres in catalonia (Spain)

2021 ◽  
Vol 52 (1) ◽  
pp. 45-57
Author(s):  
Henar González Fernández ◽  
Cristina Laborda Molla ◽  
Mercè Jariot García
Keyword(s):  
Quality Of Life ◽  
Intellectual Disability ◽  
Random Sample ◽  
Crucial Role ◽  
Personal Development ◽  
Employability Skills ◽  
Moderate Intellectual Disability ◽  
The Relationship

Background: The study explores the relationship between quality of life (QoL) and employability skills in a non-random sample of 100 employees of occupational centres (OCs) in Barcelona (Spain). The influence of gender, age and level of intellectual disability (ID) is also explored. Method: A quantitative approach was adopted to collect and examine data, gathered through two different instruments: the GENCAT SCALE (Verdugo et al., 2008) (and the Employability Skills Scale (Jariot, Laborda and González, 2020). Results: A correlation between QoL and employability skills has been found. A relationship between age and employability skills was also found, in which younger individuals reported better in employability skills. Age was also found to have an effect on some QoL domains. The ID level turned out to be a significant factor in the development of employability skills, as well as in some QoL domains. The crucial role of job placement in personal development is underlined, as well as the need for more inclusive procedures in occupancy services.

Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome

Cardiology ◽  
2017 ◽  
Vol 137 (4) ◽  
pp. 256-260 ◽  
Author(s):  
Francesca Gualandi ◽  
Fatima Zaraket ◽  
Michele Malagù ◽  
Giulia Parmeggiani ◽  
Cecilia Trabanelli ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Mutation Load ◽  
Pathogenic Variants ◽  
Digenic Inheritance ◽  
Double Heterozygosity ◽  
Death Cases ◽  
Generation Sequencing

Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient. The parents were heterozygous for each variation. This novel finding highlights the role of mutation load in Brugada syndrome and strongly suggests the adoption of a gene panel to obtain an accurate genetic diagnosis, which is mandatory for risk stratification, prevention, and therapy.

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