Contiguous hemizygous deletion ofTBX5,TBX3, andRBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes

2006 ◽  
Vol 140A (17) ◽  
pp. 1880-1886 ◽  
Author(s):  
Wiktor Borozdin ◽  
Ana M. Bravo-Ferrer Acosta ◽  
Eva Seemanova ◽  
Michael Leipoldt ◽  
Michael J. Bamshad ◽  
...  
Keyword(s):  
Hemizygous Deletion

Hemizygous deletion of CTGF/CCN2 does not suffice to prevent fibrosis of the severely injured kidney

2012 ◽  
Vol 31 (7-8) ◽  
pp. 421-431 ◽  
Author(s):  
Lucas L. Falke ◽  
Amélie Dendooven ◽  
Jan Willem Leeuwis ◽  
Tri Q. Nguyen ◽  
Rob J. van Geest ◽  
...  
Keyword(s):  
Severely Injured ◽  
Hemizygous Deletion ◽  
Injured Kidney

scholarly journals MALDI-TOF-MS Assay to Detect the Hemizygous 22q11.2 Deletion in DNA from Dried Blood Spots

2016 ◽  
Vol 62 (1) ◽  
pp. 287-292 ◽  
Author(s):  
Lisa J Kobrynski ◽  
Golriz K Yazdanpanah ◽  
Deborah Koontz ◽  
Francis K Lee ◽  
Robert F Vogt
Keyword(s):  
Dried Blood Spots ◽  
Diagnostic Methods ◽  
Deletion Syndrome ◽  
Congenital Defects ◽  
22Q11.2 Deletion ◽  
Maldi Tof Ms ◽  
Blood Spots ◽  
Maldi Tof ◽  
Hemizygous Deletion ◽  
Tof Ms

Abstract BACKGROUND A hemizygous deletion of 1.5–3 Mb in 22q11.2 causes a distinct clinical syndrome with variable congenital defects. Current diagnostic methods use fluorescent in situ hybridization (FISH) or comparative genomic hybridization by microarray to detect the deletion. Neither method is suitable for newborn screening (NBS), since they cannot be performed on dried blood spots (DBS). We developed a MALDI-TOF-MS assay that uses DBS to measure the hemizygous deletion of UFD1L, located within the 22q11.2 region. METHODS We used DBS from 54 affected patients, previously tested by FISH or microarray, and 100 cord blood samples to evaluate the performance of the MALDI-TOF-MS assay. With a single primer pair, a 97-base oligonucleotide within UFD1L was amplified, as was a sequence on chromosome 18 that differs by 2 nucleotides. A multiplexed, single-base extension reaction created allele-specific products for MALDI-TOF-MS detection. The products were spotted onto a silicon chip, and the height of the spectral peaks identified the relative amounts of target and reference gene. RESULTS The median ratio of the spectral peak for each UFD1L target:reference base was 0.96 and 0.99 for controls, compared with 0.35 and 0.53 for 22q11 deletion syndrome patients. There was 100% concordance between FISH/microarray and MALDI-TOF-MS in all patients with 22q11.2 deletion syndrome. CONCLUSIONS This method can be reliably performed with DBS and is suitable for high sample throughput. This assay may be considered for use in population-based NBS for 22q11.2 deletion.

Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with Williams syndrome

1998 ◽  
Vol 82 (1-2) ◽  
pp. 49-51 ◽  
Author(s):  
T. Nakayama ◽  
R. Matsuoka ◽  
M. Kimura ◽  
H. Hirota ◽  
K. Mikoshiba ◽  
...  
Keyword(s):  
Williams Syndrome ◽  
Syntaxin 1A ◽  
Hemizygous Deletion

Whole Genome Copy Number Variation Analysis of Chronic Lymphocytic Leukemia (CLL) Cells From Early-Intermediate Stage, High Risk CLL Patients Prior to First Treatment Reveals New Loss of Heterozygosity and Duplication Events in the CLL Genome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1265-1265
Author(s):  
Steven A. Schichman ◽  
Annjanette Stone ◽  
Maria Winters ◽  
Weleetka Carter ◽  
Lori Frederick ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Copy Number ◽  
Research Funding ◽  
Homozygous Deletion ◽  
Chromosome 12 ◽  
Whole Genome ◽  
Advisory Committees ◽  
Hemizygous Deletion ◽  
Number Variation ◽  
Trisomy 12

Abstract Abstract 1265 Poster Board I-287 Introduction Fluorescence in situ hybridization (FISH), in combination with other markers, is used as a prognostic tool for CLL patients at diagnosis. The presence or absence of trisomy 12 and deletions at 13q, 11q, and 17p helps to predict disease progression and to stratify patients for therapeutic decisions. We hypothesized that whole genome single nucleotide polymorphism (SNP)-based copy number variation (CNV) analysis would capture all of the information in current CLL FISH panels and would reveal new CNV features in the CLL genome. Patients and Methods Nineteen early-intermediate clinical stage, untreated CLL patients aged 29 to 77 were determined to be at high risk for disease progression by FISH, IgVH mutation status, ZAP-70, and CD38 prognostic markers. CLL cells and normal cells were separated by magnetic bead selection from patient peripheral blood samples with absolute lymphocyte counts that ranged from 7.4 to 162 × 109/L. CNV analysis was performed on purified genomic DNA from the CLL cells and from normal cells for each patient in order to distinguish acquired CNVs in malignant cells from polymorphic CNVs in the human genome. We used the Illumina human660w-quad beadchip, a SNP-based microarray for whole-genome genotyping and CNV analysis that contains more than 550,000 tag SNPs and approximately 100,000 additional markers that target regions of common CNV. CNV data was analyzed using CNV partition (Illumina Genome Studio software) and PennCNV. Results 100% concordance is found between del(13q), del(11q), and del(17p) FISH abnormalities and loss of heterozygosity (LOH) at 13q, 11q, and 17p by CNV analysis. All three patients with trisomy 12 by FISH show copy number(CN)=3 of chromosome 12 by CNV analysis. Of 15 patients with del(13q) by FISH, 12 out of 15 have regions of hemizygous deletion on 13q that vary from ∼830 Kb to ∼38 Mb. The smallest region of LOH is located within 13q14.3. Three out of 15 patients show homozygous deletion within 13q14.3. One of these 3 patients has copy-neutral LOH of the entire 13q arm with an embedded 835 Kb segment of homozygous deletion at 13q14.3. Two patients have large discontinuous segments of LOH on 13q, indicating complex interstitial deletion events. Two out of 5 patients with del(13q) as a sole FISH abnormality show additional CNV events in the CLL genome. One of these patients has copy neutral LOH at 2q33.1-telomere(tel). One other patient with sole del(13q) FISH shows LOH events at 10q23.31-23.33 and at 15q15.1. Five out of six patients with del(11q) by FISH have either 13q LOH (n=4) or chromosome 12 CN=3 (n=1) without any other CNV events detected in the CLL genome. One patient with trisomy 12 and del(11q) by FISH has three additional acquired CNV abnormalities in the CLL genome: LOH at 7p15.2-tel, LOH at 11p13, and CN=3 at 3q24-tel. In contrast to patients with del(11q), del(13q), and trisomy 12, patients with del(17p) by FISH have numerous acquired CNV abnormalities in the CLL genome. These include LOH events at 1p34.3-p34.2, 2q34-q36.3, 3p21.31-tel, 4p13, 4p15.1-tel, 15q11.2-q14 and 15q14-q15.3, 16p13.3-tel, 16p13.11, 16p13.2, 18p11.21-tel, 20p11.21-tel, and 20q13.2-q13.31. CN=3 at 2p12-tel is detected in 2 out of 5 patients with 17p hemizygous deletion. One out of 5 patients with 17p hemizygous deletion shows CN=3 at 10q22.2-tel. One other patient also with 17p hemizygous deletion shows CN=3 at 22q12.2-tel. Conclusions Whole genome CNV analysis by SNP-based microarrays greatly expands our ability to detect acquired genomic events in CLL cells. These events include hemizygous deletion, homozygous deletion, copy-neutral LOH, and CN=3 duplication. Detection of copy-neutral LOH is not possible by FISH or array comparative genomic hybridization technology. The current study reveals a high number of acquired CNV events in earlier stage, untreated CLL patients with 17p hemizygous deletion. This observation, indicative of genomic instability, is consistent with the known poor prognosis of del(17p) patients. The new somatic CNV abnormalities detected in CLL cells may help to discover additional genes or signaling pathways involved in CLL initiation and progression. In addition, the new CNV markers may be used in larger clinical studies to improve CLL prognosis and patient stratification for therapy. Disclosures Shanafelt: Genentech: Research Funding; Hospira: Membership on an entity's Board of Directors or advisory committees, Research Funding; Polyphenon E International: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Bayer Health Care Pharmaceuticals: Research Funding. Kay:Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding; Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees. Zent:Genentech, Bayer, Genzyme, Novartis: Research Funding.

scholarly journals Tbx1, a 22q11.2-encoded gene, is a link between alterations in fimbria myelination and cognitive speed in mice

2021 ◽  
Author(s):  
Takeshi Hiramoto ◽  
Akira Sumiyoshi ◽  
Takahira Yamauchi ◽  
Kenji Tanigaki ◽  
Qian Shi ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Copy Number Variants ◽  
Production Capacity ◽  
Loss Of Function ◽  
Structural Alterations ◽  
Cellular Basis ◽  
Hemizygous Deletion ◽  
Chromosome 22Q11.2 ◽  
Cognitive Speed ◽  
The Brain

Copy number variants (CNVs) have provided a reliable entry point to identify structural correlates of atypical cognitive development. Hemizygous deletion of human chromosome 22q11.2 is associated with impaired cognitive function; however, the mechanisms by which numerous genes encoded in this CNV contribute to cognitive deficits via diverse structural alterations in the brain remain unclear. This study aimed to determine the cellular basis of the link between alterations in brain structure and cognitive functions in a mouse model. The heterozygosity of Tbx1, a 22q11.2 gene, altered the composition of myelinated axons in the fimbria, reduced oligodendrocyte production capacity, and slowed the acquisition of spatial memory and cognitive flexibility. Our findings provide a cellular basis for specific cognitive dysfunctions that occur in patients with loss-of-function TBX1 variants and 22q11.2 hemizygous deletion.

scholarly journals Autism Spectrum Disorders: Analysis of Mobile Elements at 7q11.23 Williams–Beuren Region by Comparative Genomics

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1605
Author(s):  
Francesca Anna Cupaioli ◽  
Chiara Fallerini ◽  
Maria Antonietta Mencarelli ◽  
Valentina Perticaroli ◽  
Virginia Filippini ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Comparative Genomics ◽  
Autism Spectrum ◽  
Mobile Elements ◽  
Small Scale ◽  
Patient Stratification ◽  
Multisystem Disorder ◽  
Hemizygous Deletion ◽  
Spectrum Disorders ◽  
Behavioral Divergence

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders, characterized by a deficit in social interaction and communication. Many genetic variants are associated with ASD, including duplication of 7q11.23 encompassing 26–28 genes. Symmetrically, the hemizygous deletion of 7q11.23 causes Williams–Beuren syndrome (WBS), a multisystem disorder characterized by “hyper-sociability” and communication skills. Interestingly, deletion of four non-exonic mobile elements (MEs) in the “canine WBS locus” were associated with the behavioral divergence between the wolf and the dog and dog sociability and domestication. We hypothesized that indel of these MEs could be involved in ASD, associated with its different phenotypes and useful as biomarkers for patient stratification and therapeutic design. Since these MEs are non-exonic they have never been discovered before. We searched the corresponding MEs and loci in humans by comparative genomics. Interestingly, they mapped on different but ASD related genes. The loci in individuals with phenotypically different autism and neurotypical controls were amplified by PCR. A sub-set of each amplicon was sequenced by Sanger. No variant resulted associated with ASD and neither specific phenotypes were found but novel small-scale insertions and SNPs were discovered. Since MEs are hyper-methylated and epigenetically modulate gene expression, further investigation in ASD is necessary.

Germline Hemizygous Deletion of Gene HNF1B Associated with a Case of Severe Neonatal Cholestasis and Hepatocarcinoma

2018 ◽  
pp. 1 ◽  
Author(s):  
Cécile de Leusse ◽  
André Maues De Paula ◽  
Audrey Ascherod ◽  
Chistelle Parache ◽  
Hery Geraldine ◽  
...  
Keyword(s):  
Neonatal Cholestasis ◽  
Hemizygous Deletion

scholarly journals Handedness and corpus callosal morphology in Williams syndrome

2013 ◽  
Vol 25 (1) ◽  
pp. 253-260 ◽  
Author(s):  
Marilee A. Martens ◽  
Sarah J. Wilson ◽  
Jian Chen ◽  
Amanda G. Wood ◽  
David C. Reutens
Keyword(s):  
Corpus Callosum ◽  
Williams Syndrome ◽  
Genetic Disorder ◽  
Control Group ◽  
Structural Magnetic Resonance Imaging ◽  
Lim Kinase ◽  
Left Handed ◽  
Hemizygous Deletion ◽  
Brain Structure And Function ◽  
And Function

AbstractWilliams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

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