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Background: Copy-number variants (CNVs) of chromosome 15 have been associated with neurodevelopmental disorders like autism spectrum disorders (ASDs) and developmental delay.
Objectives
We report 6 patients with autistic features and other neurodevelopmental problems carrying CNVs of chromosome 15.
Methods
Materials and methods: The probands belong to a group of patients referred to our clinic and laboratory with autism as main feature. A complete clinical evaluation was performed with focus on neurologic, psychiatric, and psychological evaluation with specific autism tests. Array-based comparative genomic hybridization (array-CGH) was performed using 180K platform (Agilent technology).
Results
six patients investigated by array-CGH had a CNV involving chromosome 15. Four of these patients, previously reported by us (ref 1), had small duplications of 15q13.3 involving CHRNA7 and OTUD7A genes. The other two patients had large deletions of 15q21q22 and 15q24, respectively. A deletion of 15q21.2 - q22.2 was detected in one patient. The deleted region contains 62 genes and has been rarely reported in patients with neurodevelopmental disorders. A deletion of 15q24.1 - q24.2 was detected in the other patient. This region is recurrently deleted in developmentally delayed patients (ref 3).
Conclusions
Our data highlight that chromosome 15 is a hub for neurodevelopmental disorder and illustrates the utility of array-CGH in the investigation of patients with autism, specifically in the context of complex phenotypes. Acknowledgment: The research leading to these results has received funding from the EEA Grant 2014-2021, under the project contract No 6/2019. References: Genes (Basel). 2021 Jul 1;12(7):1025. https://www.omim.org/entry/618060 Clinical Genome Resource. https://dosage.clinicalgenome.org/clingen_region.cgi?id=ISCA-46296
15q11.2-q13.3 region is prone to genomic rearrangements leading to both deletions and duplications. A wide spectrum of neuropsychiatric conditions, such as developmental delay/intellectual disability (DD/ID), autism, attention-deficit hyperactivity disorder, schizophrenia, epilepsy was reported in association with genomic imbalances of this region.
Objectives
In this paper we report on 9 children carrying 15q11.2-q13.3 duplications.
Methods
Seven boys and two girls, aged 15 months to 15 years, were included in the study. Genomic investigations were carried out by array-based comparative genomic hybridization (Agilent Technologies). In all patients the psychomotor development, dysmorphic features, neuroimaging and EEG anomalies were assessed. Psychologic and psychiatric evaluation was performed with specific tests.
Results
The size of the duplications ranged from 9.65 Mb to 0.38 Mb. All patients presented speech delay. Autistic behavior and muscular hypotonia were detected in 8 out of 9 patients, DD/ID in 6. Two children presented epileptic seizures, in addition 4 other children had EEG anomalies. Facial dysmorphic features were observed in 5 patients. Neuroimaging studies showed anomalies in 4 children. The smallest region of overlap in our patient group harbors CHRNA7 gene, a candidate for the behavioral abnormalities.
Conclusions
15q duplications encompassing CHRNA7 gene were associated with different neuropsychiatric features in our patients. Our results further support the association of 15q duplications with neuropsychiatric phenotypes, with clinical heterogeneity and variable severity, which is yet to be explained. Acknowledgment: The research leading to these results has received funding from the EEA RO NO Grant 2014-2021, the project contract No 6/2019.
Brain heterotopia represent a group of rare malformations with a heterogeneous phenotype, ranging from asymptomatic to severe clinical picture (resistant epilepsy, severe developmental delay). The etiology is multifactorial, including both genetic and environmental factors.
Objectives
In this paper we present our experience regarding behavior problems in patients with heterotopia.
Methods
A cohort of 16 pediatric patients with brain heterotopia, six females and ten males, with age at last follow-up ranging from 2 months to 24 years were investigated by clinical examination, electroencephalographic studies, brain imaging, and genomic tests. Specific psychological tests and psychiatric evaluation were performed in all children for behavior problems assessment.
Results
Six individuals presented behavioral problems: autism (three patients) and hyperkinesia with attention deficit (three patients). All of them had intellectual disability or learning problems; five patients had epilepsy, with drug-resistant seizures in four cases. In two cases the behavioral problems occurred before the onset of epileptic seizures.
Conclusions
Behavior problems are important features in patients with brain heterotopia, making the management of these patients more difficult, especially when they occur in association with drug-resistant epilepsy. Acknowledgements: This work was supported partially by grants of the Romanian National Authority for Scientific Research and Innovation CCCDI – UEFISCDI, Projects COFUND-ERANET E-RARE 3-HETER-OMICS-2 Number 87/2019 and 88/2019 within PNCDI III.
Disclosure
No significant relationships.
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