Clinical and molecular characterization of patients with 16p11.2 microdeletion syndrome
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PROVIDER: PRJNA667734 | ENA |
REPOSITORIES: ENA
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Project description:The study presents three cases of patients with deletions within 16p11.2 regions. Every child had characteristic craniofacial dysmorphic features and hand or feet abnormalities. The first proband had additionally obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism and café au lait spots. The second proband suffered from cardiac, pulmonary and hematological problems. The third proband had motor delay, bronchial asthma and umbilical hernia. Although each patient presented characteristic features of the syndrome, children differed in clinical pictures among themselves. The genetic diagnosis of the 16p11.2 deletion syndrome was made in children at different age, based on the multiplex ligation probe-dependent amplification (MLPA) analysis and/or microarrays methods. This study highlights the impact of the size of deleted regions, as they may affect the clinical picture of patients with 16p11.2 microdeletion syndrome. Reported cases indicates the key role of the interdisciplinary approach in 16p11.2 microdeletion syndrome diagnostics, as the care of patients with this deletion is based on regular health assessment and adjustment of the nervous system development therapy
2020-10-07 | GSE159129 | GEO
Project description:We described the clinical and molecular data of a patient with a 19p13.3 microdeletion detected by using high-resolution SNP-array
2016-09-29 | E-MTAB-4760 | biostudies-arrayexpress
Project description:Molecular cytogenetic techniques such as microarray analysis have allowed for a “genotype-first” approach to the characterization of chromosome abnormalities: in the absence of clinical features suggestive of a specific syndrome, patients with similar copy number imbalances can be examined for common clinical features. Using a genotype-first approach, we characterized microdeletions at 20q13.33 in six patients referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. These deletions are relatively rare, with only 11 cases reported. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. Based on analysis of the smallest region of overlap (SRO) among cases reported here and in previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4, KCNQ2, and MYT1. Deletion of this region may play an important role in cognitive development. aCGH control vs. patient, total of 6 patients
2010-12-31 | E-GEOD-21536 | biostudies-arrayexpress
Project description:Molecular cytogenetic techniques such as microarray analysis have allowed for a “genotype-first” approach to the characterization of chromosome abnormalities: in the absence of clinical features suggestive of a specific syndrome, patients with similar copy number imbalances can be examined for common clinical features. Using a genotype-first approach, we characterized microdeletions at 20q13.33 in six patients referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. These deletions are relatively rare, with only 11 cases reported. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. Based on analysis of the smallest region of overlap (SRO) among cases reported here and in previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4, KCNQ2, and MYT1. Deletion of this region may play an important role in cognitive development.
2010-12-31 | GSE21536 | GEO
Project description:Background: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities and so on. However, the prenatal phenotypes of 16p11.2 copy number variations (CNVs) are still not well described till now. This study aimed to provide an elaborate summary of intrauterine phenotypic features for such genomic disorders. Methods: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions after birth for all cases were followed up. Meanwhile, we made a pooled analysis on the prenatal phenotypes for the published cases carrying 16p11.2 CNVs. Results: 20 fetuses (20/20884, 0.10%) with 16p11.2 CNVs were identified: five 16p11.2 BP2-BP3 deletion, ten 16p11.2 BP4-BP5 deletion and five 16p11.2 BP4-BP5 duplication. Abnormal ultrasound findings were recorded in ten participants with 16p11.2 deletions.Various degrees of intrauterine phenotypic features, ranging from normal to abnormal, were observed. No ultrasound abnormalities were observed for all 16p11.2 duplication cases during the pregnancy period. For 16p11.2 deletions, eleven cases terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except one was lost to follow up. Conclusions: Diverse prenatal phenotypes were presented in 16p11.2 CNVs, ranging from normal to abnormal. For 16p11.2 BP4-BP5 deletion, the most common structural and non-structural abnormalities were the abnormality of the vertebral column or rib and thickened nuchal translucency, respectively. 16p11.2 BP2-BP3 deletion might be closely associated with fetal growth restriction and single umbilical artery. No representative ultrasound findings for 16p11.2 duplication were observed till now. Considering the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long term follow up after birth should be carried out for these cases. We identified 20 fetuses carrying the 16p11.2 microdeletions and microduplications using chromosomal microarray analysis. And diverse prenatal phenotypes and the critical genes involved in the deleted/duplicated regions were described in this study.
2024-04-29 | GSE265911 | GEO
Project description:While the neuronal underpinnings of autism spectrum disorders (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2df/+ mouse model of 16p11.2 deletion ASD syndrome. We discovered that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2df/+ mice, endothelial dysfunction resulted in impaired cerebral angiogenesis at postnatal day (P) 14, and in altered neurovascular coupling and cerebrovascular reactivity at P50. Moreover, we showed defective angiogenesis in primary 16p11.2df/+ mouse brain endothelial cells and in iPSC-derived endothelial cells from human 16p11.2 deletion carriers. Finally, we found that mice with endothelium-specific 16p11.2 deletion (16p11.2DEC) partially recapitulated some behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.
2020-04-03 | GSE147790 | GEO
Project description:Prenatal phenotypes and pregnancy outcomes of fetuses with 16p11.2 microdeletion/microduplication
| PRJNA1104671 | ENA
Project description:The 600kb BP4-BP5 16p11.2 CNV (copy number variant) is associated with neuroanatomical, neurocognitive and metabolic disorders. These recurrent rearrangements are associated with reciprocal phenotypes such as obesity and underweight, macro- and microcephaly, as well as autism spectrum disorder (ASD) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal CNVs in 16p11.2. The genome-wide transcript perturbations correlated with clinical endophenotypes of the CNV and were enriched for genes associated with ASD. We uncovered a significant correlation between copy number changes and expression levels of genes mutated in ciliopathies. Transcriptome profiles of lymphoblastoid cell lines of 50 16p11.2 deletion carriers, 31 16p11.2 duplication carriers and 17 controls.
2015-05-10 | E-GEOD-57802 | biostudies-arrayexpress
Project description:BackgroundThe recurrent ∼ 600 kb 16p11.2 microdeletion is among the most commonly known genetic etiologies of autism spectrum disorder, overweightness, and related neurodevelopmental disorders.Case presentationOur patient is a 2-year-old white girl from the first pregnancy of a non-consanguineous healthy young white couple (father 33-years old and mother 29-years old). Our patient and her parents' DNA were analyzed by comparative genomic hybridization-array platform. Comparative genomic hybridization-array analysis highlighted a ∼ 600 kb deletion in 16p11.2 region. It has a segregant nature, since it was found in the mother and in her 2-year-old daughter. The microdeletion was confirmed by fluorescence in situ hybridization analysis.ConclusionsThe presented clinical case is worthy of note since the observed microdeletion is often associated with a clinical phenotype tending to overweightness, but the proband (female) was hospitalized due to poor height and weight development, and anorexia. Moreover, the segregant nature of the observed genomic abnormality has to be noted, as well as the phenotypic variability between the mother and daughter. The case described here enriches the phenotypical spectrum linked to the 16p11.2 microdeletion. For these reasons, in the presence of a suspected genetic pathology it is fundamental to study the proband from the clinical point of view, to extend the clinical observation to the parents, and to provide a good family anamnesis. In this way, it is possible to reveal the presence of a familial genetic pathology whose phenotypical outcomes can be highly variable among the members of a family.
| S-EPMC5881179 | biostudies-literature
Project description:Single cell transcriptome analysis of the effect of the 16p11.2 microdeletion on hIPSC derived developing human GABAergic neurons
| PRJEB46758 | ENA