Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Severe intellectual disability and autistic features associated with microduplication 2q23.1.

ABSTRACT: We report on two patients with developmental delay, hypotonia, and autistic features associated with duplications of chromosome region 2q23.1-2q23.2 detected by chromosome microarray analysis. The duplications include one OMIM Morbid Map gene, MBD5, as well as seven known RefSeq genes (ACVR2A, ORC4L, EPC2, KIF5C, MIR1978, LYPD6B, and LYPD6). MBD5 lies in the minimum area of overlap of the 2q23.1 microdeletion syndrome. This report provides the first detailed clinical examination of two individuals with a duplication of this region and suggests that brain development and cognitive function may be affected by an increased dosage of the genes involved.

SUBMITTER: Chung BH

PROVIDER: S-EPMC3306850 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Severe intellectual disability and autistic features associated with microduplication 2q23.1.

Chung Brian H Y BH Mullegama Sureni S Marshall Christian R CR Lionel Anath C AC Weksberg Rosanna R Dupuis Lucie L Brick Lauren L Li Chumei C Scherer Stephen W SW Aradhya Swaroop S Stavropoulos D James DJ Elsea Sarah H SH Mendoza-Londono Roberto R

European journal of human genetics : EJHG 20111116 4

We report on two patients with developmental delay, hypotonia, and autistic features associated with duplications of chromosome region 2q23.1-2q23.2 detected by chromosome microarray analysis. The duplications include one OMIM Morbid Map gene, MBD5, as well as seven known RefSeq genes (ACVR2A, ORC4L, EPC2, KIF5C, MIR1978, LYPD6B, and LYPD6). MBD5 lies in the minimum area of overlap of the 2q23.1 microdeletion syndrome. This report provides the first detailed clinical examination of two individua ...[more]

PMID: 22085900

Similar Datasets

A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features.

Project description:No data on interstitial microduplications of the 16q24.2q24.3 chromosome region are available in the medical literature and remain extraordinarily rare in public databases. Here, we describe a boy with a de novo 16q24.2q24.3 microduplication at the Single Nucleotide Polymorphism (SNP)-array analysis spanning ~2.2 Mb and encompassing 38 genes. The patient showed mild-to-moderate intellectual disability, speech delay and mild dysmorphic features. In DECIPHER, we found six individuals carrying a "pure" overlapping microduplication. Although available data are very limited, genomic and phenotype comparison of our and previously annotated patients suggested a potential clinical relevance for 16q24.2q24.3 microduplication with a variable and not (yet) recognizable phenotype predominantly affecting cognition. Comparing the cytogenomic data of available individuals allowed us to delineate the smallest region of overlap involving 14 genes. Accordingly, we propose ANKRD11, CDH15, and CTU2 as candidate genes for explaining the related neurodevelopmental manifestations shared by these patients. To the best of our knowledge, this is the first time that a clinical and molecular comparison among patients with overlapping 16q24.2q24.3 microduplication has been done. This study broadens our knowledge of the phenotypic consequences of 16q24.2q24.3 microduplication, providing supporting evidence of an emerging syndrome.

| S-EPMC7349372 | biostudies-literature

Familial 1q22 microduplication associated with psychiatric disorders, intellectual disability and late-onset autoimmune inflammatory response.

Project description:BackgroundDespite the extensive use of chromosomal microarray technologies in patients with neurodevelopmental disorders has permitted the identification of an increasing number of causative submicroscopic rearrangements throughout the genome, constitutional duplications involving chromosome 1q22 have seldom been described in those patients.ResultsWe report on a pedigree with seven affected members showing varying degrees of behavioural and emotional disturbances including general anxiety disorder, mood disorders, and intellectual disability. Two adult female patients also showed late onset autoimmune inflammatory responses characterized by alopecia, skin ulcers secondary to inflammatory vasculitis, interstitial lung disease, and Raynaud's phenomenon. Array-CGH analysis identified in the affected individuals a 290 Kb microduplication in the chromosome 1q22. The rearrangement involves eleven known genes and is not present in the databases of polymorphic copy number variants.ConclusionsThe rearrangement segregates with the neurological clinical features observed in our patients, suggesting that dosage imbalance of one or more genes in this genomic region may lead to the observed phenotype. The association between the microduplication and the inflammatory disease is much less evident. Additional reported patients carrying similar microduplications are needed to clarify this aspect.

| S-EPMC4276019 | biostudies-literature

BCL11A associated intellectual disability

Project description:This data has been described in the following article: Dias et al., American Journal of Human Genetics, 2016, and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute(including information on acknowledgement), please see http://www.sanger.ac.uk/datasharing/

2016-07-12 | E-ERAD-520 | biostudies-arrayexpress

Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy.

Project description:We report on two consanguineous sibs affected with severe intellectual disability and autistic features due to a homozygous missense variant of GRIN1. Massive parallel sequencing was performed using a gene panel including 450 genes related to intellectual disability and autism spectrum disorders. We found a homozygous missense variation of GRIN1 (c.679G>C; p.(Asp227His)) in the two affected sibs, which was inherited from both unaffected heterozygous parents. Heterozygous variants of GRIN1, encoding the GluN1 subunit of the NMDA receptor, have been reported in patients with neurodevelopmental disorders including epileptic encephalopathy, severe intellectual disability, and movement disorders. The p.(Asp227His) variant is located in the same aminoterminal protein domain as the recently published p.(Arg217Trp), which was found at the homozygous state in two patients with a similar phenotype of severe intellectual disability and autistic features but without epilepsy. In silico predictions were consistent with a deleterious effect. The present findings further expand the clinical spectrum of GRIN1 variants and support the existence of hypomorphic variants causing severe neurodevelopmental impairment with autosomal recessive inheritance.

| S-EPMC5315503 | biostudies-literature

Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features.

Project description:The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol. This study suggests a role for AA-containing phosphatidylinositols in the development of ID accompanied by epilepsy and autistic features.

| S-EPMC5065650 | biostudies-literature

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability.

Project description:Sub-threshold autistic traits are common in the general population. Children with sub-threshold autistic traits have difficulties with social adaptation. Contactin-associated protein-like 2 (CNTNAP2) is associated with the development of Autism spectrum disorder (ASD) and the single-nucleotide polymorphism rs2710102 (G/A) of CNTNAP2 is suggested to contribute to sub-threshold social impairments and intellectual disabilities. We recruited 67 children with Autistic disorder (AD) (49 boys, 18 girls, aged 38-98 months) and 57 typically developing (TD) children (34 boys, 23 girls, aged 53-90 months). We assessed the participants' intelligence and social reciprocity using the Kaufman Assessment Battery for Children (K-ABC) and the Social Responsiveness Scale (SRS), respectively. Genomic DNA was extracted from the buccal mucosa and genotyped for rs2710102. A chi-square test revealed a significant association between genotype and group [χ2(2) = 6.56, p = 0.038]. When a co-dominant model was assumed, the results from linear regression models demonstrated that TD children with A-carriers (AA + AG) presented higher SRS T-scores [t(55) = 2.11, p = 0.039] and lower simultaneous processing scale scores of K-ABC [t(55) = -2.19, p = 0.032] than those with GG homozygotes. These associations were not significant in children with ASD. TD children with the rs2710102 A-allele may have more sub-threshold autistic traits than those with GG homozygotes, reflected in higher SRS scores and lower simultaneous processing scale scores. These results support the use of genetic evidence to detect sub-threshold autistic traits.

| S-EPMC8668106 | biostudies-literature

Microduplication in the 2p16.1p15 chromosomal region linked to developmental delay and intellectual disability.

Project description:Background:Several patients with the 2p16.1p15 microdeletion syndrome have been reported. However, microduplication in the 2p16.1p15 chromosomal region has only been reported in one case, and milder clinical features were present compared to those attributed to 2p16.1p15 microdeletion syndrome. Some additional cases were deposited in DECIPHER database. Case presentation:In this report we describe four further cases of 2p16.1p15 microduplication in four unrelated probands. They presented with mild gross motor delay, delayed speech and language development, and mild dysmorphic features. In addition, two probands have macrocephaly and one a congenital heart anomaly. Newly described cases share several phenotype characteristics with those detailed in one previously reported microduplication case. Conclusion:The common features among patients are developmental delay, speech delay, mild to moderate intellectual disability and unspecific dysmorphic features. Two patients have bilateral clinodactyly of the 5th finger and two have bilateral 2nd-3rd toes syndactyly. Interestingly, as opposed to the deletion phenotype with some cases of microcephaly, 2 patients are reported with macrocephaly. The reported cases suggest that microduplication in 2p16.1p15 chromosomal region might be causally linked to developmental delay, speech delay, and mild intellectual disability.

| S-EPMC6011332 | biostudies-literature

EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.

Project description:Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. The EIF2S3 gene encodes the ? subunit of eukaryotic translation initiation factor 2 (eIF2), crucial for initiation of protein synthesis and regulation of the ISR. Studies in patient fibroblasts confirm increased ISR activation due to the Ile465Serfs mutation and functional assays in yeast demonstrate that the Ile465Serfs mutation impairs eIF2? function to a greater extent than tested missense mutations, consistent with the more severe clinical phenotype of the Ile465Serfs male mutation carriers. Thus, we propose that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms.

| S-EPMC6267786 | biostudies-literature

Severe Intellectual Disability Associated with Recessive Defects in CNTNAP2 and NRXN1.

Project description:While heterozygous variants in CNTNAP2 and NRXN1 are reported as susceptibility factors for neuropsychiatric disorders, homozygous or compound heterozygous defects in either gene were reported as causative for severe neurodevelopmental disorders. This review provides an overview of the clinical aspects in patients with recessive defects in CNTNAP2 and NRXN1.

| S-EPMC3366709 | biostudies-literature

Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability.

Project description:Intellectual disability is a common condition that carries lifelong severe medical and developmental consequences. The causes of intellectual disability (ID) remain unknown for the majority of patients due to the extensive clinical and genetic heterogeneity of this disorder. De novo mutations may play an important role in ID as most individuals with ID present as isolated cases without family history and/or clear syndromic indication. In addition, the involvement of such mutations have recently been demonstrated in a small number of individuals with ID. Here we evaluate the diagnostic potential and role of de novo mutations in a cohort of 100 patients with ID of unknown cause using family-based exome sequencing. Single end short-read (50 bp) SOLiD 4 sequencing data for 300 individuals, constituting 100 patient-parent trios. For more details please read; http://www.nejm.org/doi/full/10.1056/NEJMoa1206524. Dataset is created by RUNMC (Radboud University, Nijmegen Medical Center), partner of Geuvadis consortium (http://www.geuvadis.org).

2013-11-06 | E-GEUV-5 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data