Interstitial deletion of 18q: Comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33)

Kato, Zenichiro; Morimoto, Wataru; Kimura, Takeshi; Matsushima, Akihiro; Kondo, Naomi

doi:10.1002/bdra.20633

Cited by 20 publications

(19 citation statements)

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“…Behaviour will also be influenced by interactions within social and learning environments and by reactions from that environment to the individual's tempera- [6][7][8][9][10][11]13,14,[30][31][32][33][34][35] Published cases with proven TCF4 mutations [6][7][8][9][10][11]13,14,[30][31][32][33][34][35] Present study ment, external features, and neuropsychological deficits. Studying phenotypes of rare and ultra-rare genetic syndromes associated with severe intellectual disability has made it clear that, although individual outcomes may arise from genetic differences, the expression of genes affecting structure, development and function of the brain is also influenced by the interplay between genes, learning, and social context, and too much emphasis on biological determinants should be avoided.…”

Section: Discussionmentioning

confidence: 96%

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Balkom

Vuijk²,

Franssens

et al. 2012

Develop Med Child Neuro

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ABBREVIATIONSASD Autism spectrum disorder PTHS Pitt-Hopkins syndrome AIM The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt-Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).METHOD The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.RESULTS All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.INTERPRETATION Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.Pitt-Hopkins syndrome (PTHS) is characterized by intellectual disability, distinctive facial characteristics, breathing abnormalities, and repetitive behaviours. It is caused by genetic deletions ⁄ mutations resulting in TCF4 haploinsufficiency. To date, some 66 patients with confirmed TCF4 changes have been studied worldwide, mainly investigating somatic and genetic aspects.Early descriptions of PTHS in individuals with intellectual disability emphasized an abnormal breathing pattern, distinctive facial features, and postnatal microcephaly. Further definition of the PTHS phenotype in later publications included severe developmental delays in motor and speech ⁄ language development, episodic diurnal hyperventilation with apnoea, and frequent epilepsy.1-5 Three causes of PTHS have been identified. The dominant form of PTHS is caused by deletions ⁄ mutations in Transcription Factor 4 (TCF4) on chromosome 18 at 18q21. [6][7][8][9][10][11][12][13][14] Recessive forms of a PTHS-like disorder are caused by mutations in NeuReXiN1 (NRXN1) on chromosome 2 and CoNTactiN Associated Protein-like 2 (CNT-NAP2) on chromosome 7. 15,16 As studies of the syndrome have accumulated, it has become clear that not all individuals with molecularly confirmed alterations show intermittent overbreathing. Most studies of individuals with PTHS have reported severe developmental delay and intellectual disability, motor abnormalities (late or absent walking, repetitive movements of hands and head), and behavioural traits such as autistic symptoms; a quiet, friendly disposition in ...

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Section: Discussionmentioning

confidence: 96%

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Balkom

Vuijk²,

Franssens

et al. 2012

Develop Med Child Neuro

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“…MRI findings have been reported from 67 patients and of these 24 (36%) were normal [Zweier et al, 2007[Zweier et al, , 2008Giurgea et al, 2008;de Pontual et al, 2009;Rosenfeld et al, 2009;Kato et al, 2010;Taddeucci et al, 2010;Takano et al, 2010;Brockschmidt et al, 2011;Marangi et al, 2011]. Most common abnormal findings reported are hypoplastic/thin corpus callosum, often more pronounced in the rostral parts, and enlarged ventricles.…”

Section: Clinical Descriptionmentioning

confidence: 95%

“…features and major types of TCF4 gene mutations found in 77 molecularly confirmed patients aged 11 months to 29 years [Peippo et al, 2006;Amiel et al, 2007;Brockschmidt et al, 2007;Zweier et al, 2007Zweier et al, , 2008Zweier et al, , 2009Andrieux et al, 2008;Giurgea et al, 2008;de Pontual et al, 2009;Rosenfeld et al, 2009;Kato et al, 2010;Taddeucci et al, 2010;Takano et al, 2010;Stavropoulos et al, 2010;Lehalle et al, 2011;Marangi et al, 2011].…”

Section: Clinical Descriptionmentioning

confidence: 99%

Pitt-Hopkins Syndrome

Peippo

Ignatius

2011

Mol Syndromol

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a Pitt-Hopkins-like phenotype has been assigned to autosomal recessive mutations of the CNTNAP2 gene at 7q33q36 and the NRXN1 gene at 2p16.3. Copyright © 2011 S. Karger AG, Basel History of the SyndromeIn 1978, pediatrician David Pitt and pediatric neurologist Ian Hopkins at the Royal Children's Hospital in Melbourne described 2 unrelated children with severe intellectual disability who while awake had spells of rapid overbreathing followed by holding of breath until cyanosis [Pitt and Hopkins, 1978]. Both patients had almost identical facial features with a wide mouth and palate, thick fleshy lips and a broad beaked nose with flared nostrils, and both also had clubbing of fingers and toes. The patients had been ascertained as a part of an etiological survey of 782 intellectually disabled individuals [Pitt and Roboz, 1965]. Over the next 28 years, only 4 sporadic patients [Singh 1993;Van Balkom et al., 1998;Peippo et al., 2006] and 1 pair of sibs [Orrico et al., 2001] supposed to have the same syndrome were published.In 2007, 2 independent groups using molecular karyotyping identified a microdeletion at 18q21.2 in 2 PittHopkins syndrome (PTHS) patients and subsequently haploinsufficiency of the TCF4 gene was found to cause the syndrome [Amiel et al., 2007;Zweier et al., 2007]. The original patients of Pitt and Hopkins [1978] and the one described by Singh [1993] were no longer available for Key WordsApnea ؒ Constipation ؒ Deletion of 18q ؒ Epilepsy ؒ Happy disposition ؒ Hyperpnea ؒ Myopia ؒ Pitt-Hopkins syndrome ؒ Stereotypic movements ؒ TCF4 Abstract Pitt-Hopkins syndrome (PTHS, MIM #610954) is characterized by severe intellectual disability, typical facial features and tendency to epilepsy, panting-and-holding breathing anomaly, stereotypic movements, constipation, and high myopia. Growth is normal or only mildly retarded, but half of the patients have postnatal microcephaly. Remarkably, congenital malformations are practically nonexistent. The cause of PTHS is de novo haploinsufficiency of the TCF4 gene (MIM * 602272) at 18q21.2. Altogether 78 PTHS patients with abnormalities of the TCF4 gene have been published since 2007 when the etiology of PTHS was revealed. In addition, 27 patients with 18q deletion encompassing the TCF4 gene but without given PTHS diagnosis have been published, and thus, the number of reported patients with a TCF4 abnormality exceeds 100. The mutational spectrum includes large chromosomal deletions encompassing the whole TCF4 gene, partial gene deletions, frameshift (including premature stop codon), nonsense, splice site, and missense mutations. So far, almost all patients have a private mutation and only 2 recurrent mutations are known. There is no evident genotype-phenotype correlation. No familial cases have been reported. Diagnosis of PTHS is based on the molecular confirmation of the characteristic clinical features. Recently,

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“…Thus, MBD1 is considered an autism-associated gene (SFARI Gene database, see sfari .org/resources/sfari-gene). Deletion of chromosome 18q21 containing MBD1 gene is also associated with mental retardation (Feenstra et al 2007;Kato et al 2010). With the progress of genetic diagnosis and sequencing efficiency, it is likely that additional MBD1 mutations or polymorphisms will be discovered.…”

Section: Genetics and Epigenetics In Adult Neurogenesismentioning

confidence: 99%

Genetics and Epigenetics in Adult Neurogenesis

Hsieh

Zhao

2016

Cold Spring Harb Perspect Biol

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The cellular basis of adult neurogenesis is neural stem cells residing in restricted areas of the adult brain. These cells self-renew and are multipotent. The maintenance of "stemness" and commitment to differentiation are tightly controlled by intricate molecular networks. Epigenetic mechanisms, including chromatin remodeling, DNA methylation, and noncoding RNAs (ncRNAs), have profound regulatory roles in mammalian gene expression. Significant advances have been made regarding the dynamic roles of epigenetic modulation and function. It has become evident that epigenetic regulators are key players in neural-stemcell self-renewal, fate specification, and final maturation of new neurons, therefore, adult neurogenesis. Altered epigenetic regulation can result in a number of neurological and neurodevelopmental disorders. Here, we review recent discoveries that advance our knowledge in epigenetic regulation of mammalian neural stem cells and neurogenesis. Insights from studies of epigenetic gene regulation in neurogenesis may lead to new therapies for the treatment of neurodevelopmental disorders.

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Interstitial deletion of 18q: Comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33)

Cited by 20 publications

References 18 publications

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Pitt-Hopkins Syndrome

Genetics and Epigenetics in Adult Neurogenesis

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