Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

BACKGROUND: Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. METHODS: Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. RESULTS: This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. CONCLUSION: This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion

Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study.

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case-control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.Clinical TrialComparative StudyControlled Clinical TrialJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Transtorno de humor bipolar: diversas apresentações de uma mesma doença Bipolar mood disorder: different occurrences of the same disease

O presente relato tem por objetivo acompanhar a evolução de um caso que se apresentou como mutismo seletivo e evoluiu para transtorno de humor bipolar e chamar atenção para a diversidade de sintomas possíveis no transtorno de humor. Em geral, o mutismo seletivo tem início na idade pré-escolar, porém os sintomas chamam mais atenção na idade escolar. A importância do diagnóstico e tratamento precoces reside na prevenção das complicações, tais como distúrbios no desenvolvimento social e acadêmico e na auto-estima, além da possibilidade de evolução para outros transtornos de ansiedade. O transtorno de humor bipolar é uma doença mental caracterizada por variações extremas no humor. Na criança, prejudica o crescimento emocional e seu desenvolvimento. É confundido com transtorno de déficit de atenção/hiperatividade e transtornos de comportamento, tais como transtorno de conduta e desafiador opositivo. A paciente do sexo feminino, quando avaliada, estava com 5 anos e 9 meses de idade. Concluiu-se o diagnóstico como mutismo seletivo. Foi indicada psicoterapia, com orientações aos pais e à escola, e iniciado o uso de inibidores seletivos de recaptação da serotonina, com boa resposta aos sintomas de ansiedade, mas passou a apresentar piora significativa do comportamento. Foi levantada a hipótese diagnóstica de transtorno de humor bipolar de início precoce. Medicada com estabilizador, apresentou adequação na terceira medicação e evolução satisfatória. O mutismo seletivo, considerado um transtorno de ansiedade na infância, pode ser pródromo para outros quadros psiquiátricos na infância. Há necessidade que os pediatras, médicos que primeiro acessam essas crianças, assim como os psiquiatras da infância, estejam atentos à riqueza de sintomas que pode dar seguimento ao quadro.<br>The purpose of the present case report is to follow the evolution of a child who presented selective mutism and evolved into bipolar mood disorder, and also to draw attention to the diversity of possible symptoms of mood disorders. In general, selective mutism starts at preschool age, although the symptoms are more evident at school age. The importance of an early diagnosis and treatment lies in the prevention of some complications, such as social and academic development and self-esteem, besides the possibility of the development of other anxiety disorders. Bipolar mood disorder is a mental disease characterized by extreme mood variations. In childhood, it hinders the child's emotional growth and development. Selective mutism is mistaken by attention deficit hyperactivity disorder, and behavioral disorders, such as conduct disorder and oppositional defiance disorder. The present case report is about a female patient evaluated at 5 years and 9 months of age. We concluded the case as being a selective mutism disorder. Not only psychotherapy, with parent and school orientation, but also medication was prescribed. The first prescribed medication was use of selective serotonin reuptake inhibitors with good results regarding anxiety symptoms, although the patient started to present significant deterioration in behavior. Because of that, the diagnostic hypothesis came to be bipolar mood disorder with an early start. The patient presented satisfactory evolution only after given a third option of mood stabilizer medication. Selective mutism, which is an anxiety disorder in childhood, can be prodromus to other psychiatric conditions at the same age. It is necessary for pediatricians, who are the doctors that first assess these children, and also child psychiatrists, to be aware of the wealth of symptoms that can give continuation to the condition