Duplication of the 15q11-q13 region: Clinical and genetic study of 30 new cases

Ageeli, Essam Al; Drunat, Séverine; Delanoë, Catherine; Perrin, Laurence; Baumann, Clarisse; Capri, Yline; Fabre-Teste, Jennifer; Aboura, Azzedine; Dupont, Céline; Auvin, Stéphane; Khattabi, Laïla El; Chantereau, Dominique; Moncla, Anne; Tabet, Anne‐Claude; Verloès, Alain

doi:10.1016/j.ejmg.2013.10.008

Cited by 71 publications

(82 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutations resulting in loss-of-function in the maternally expressed copy of UBE3A causes AS, a severe developmental disorder characterized by delayed development, intellectual disability, severe speech impairment, and ataxia (Kishino et al, 1997). Maternal duplication of UBE3A results in Dup15q syndrome, a developmental disorder that has many similarities with AS but also exhibits several autistic traits (Cook et al, 1997; Wang et al, 2008; Hogart et al, 2010; Smith et al, 2011; Urraca et al, 2013; Al Ageeli et al, 2014; Germain et al, 2014). Coincidently, several genome-wide studies from individuals with autism identify UBE3A as an autism-risk gene (Nurmi et al, 2001; Glessner et al, 2009; Schaaf et al, 2011; Kelleher et al, 2012; Carvill et al, 2013; Iossifov et al, 2014; Yuen et al, 2015).…”

Section: Specific Syndromic Disorder Related Genesmentioning

confidence: 99%

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

Lin

Frei

Kilander

et al. 2016

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families.

show abstract

Section: Specific Syndromic Disorder Related Genesmentioning

confidence: 99%

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

Lin

Frei

Kilander

et al. 2016

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…For instance, duplications on chromosome 15q11-q13 ('Dup15q syndrome') confer a very high risk for global developmental delay, hypotonia, ASD, ADHD, and epilepsy [49][50][51]. Quite notably, a subgroup of children with Dup15q syndrome exhibit a classic EEG pattern of excessive beta (12-30 Hz) frequency activity, a feature often found in patients treated with GABAergic medications such as benzodiazepenes [52]. This signature in Dup15q syndrome likely reflects the upregulation of several GABA receptor genes located in the duplicated region.…”

Section: Diagnostic Biomarkers In Autism Spectrum Disordermentioning

confidence: 99%

Electrophysiological biomarkers of diagnosis and outcome in neurodevelopmental disorders

Jeste¹,

Frohlich²,

Loo³

2015

Current Opinion in Neurology

137

104

View full text Add to dashboard Cite

“…This lack of correlation could be due to additional factors such as presence of mosaicism in Patient 2, genetic background, epigenetic modifications, and gender. Aside from the increase in gene dosage and the parental origin of the duplicated genes, additional alterations at the epigenetic level could influence gene expression, which could lead to phenotypic variability for patients who carry duplications of the same size and dosage [21,24]. Hogart et al provided some supporting evidence when they measured the level of 10 transcripts within the 15q11-13 region in two postmortem brains and found that the expression pattern correlated with parental gene dosage in the male patient.…”

Section: Discussionmentioning

confidence: 99%

Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern

et al. 2014

View full text Add to dashboard Cite

BackgroundThe 15q11-q13 region contains many low copy repeats and is well known for its genomic instability. Several syndromes are associated with genomic imbalance or copy-number-neutral uniparental disomy. We report on two patients: Patient 1 is a boy with developmental delay and autism; and Patient 2 is a girl with developmental delay, hypotonia and dysmorphism. We performed analyses to delineate their dosage in the 15q region, determine whether the patients’ dosage correlates with phenotypic severity, and whether genes in the amplified regions are significantly associated with identified functional networks.ResultsFor the proximal region of 15q, molecular cytogenetic analysis with Agilent oligonucleotide array showed a copy number of 3 for Patient 1 and a copy number of 4 for Patient 2. Fluorescent in situ hybridization analysis of Patient 2 showed two different populations of cells with different marker chromosomes. Methylation analysis of the amplified region showed that the extra copies of small nuclear ribonucleoprotein polypeptide N gene were of maternal origin. Phenotypic severity did not correlate with the size and dosage of 15q, or whether the amplification is interstitial or in the form of a supernumerary marker. Pathway analysis showed that in Patient 2, the main functional networks that are affected by the genes from the duplicated/triplicated regions are developmental disorder, neurological disease and hereditary disease.ConclusionsThe 15q11-q13 gains that were found in both patients could explain their phenotypic presentations. This report expands the cohort of patients for which 15q11-q13 duplications are molecularly characterized.

show abstract

Duplication of the 15q11-q13 region: Clinical and genetic study of 30 new cases

Cited by 71 publications

References 47 publications

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

Electrophysiological biomarkers of diagnosis and outcome in neurodevelopmental disorders

Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern

Contact Info

Product

Resources

About