Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical and molecular characterization of a patient with a combination of a deletion and a duplication of 22q13 using array CGH.

ABSTRACT: Phelan-McDermid syndrome is caused by the loss of terminal regions of different sizes at 22q13. There is a wide range of severity of symptoms in patients with a 22q13 deletion, but these patients usually show neonatal hypotonia, global developmental delay, and dysmorphic traits. We carried out a clinical and molecular characterization of a patient with neonatal hypotonia and dysmorphic features. Array-based comparative genomic hybridization showed an 8.24 Mb terminal deletion associated with a 0.20 Mb duplication. Characterization of patients with Phelan-McDermid syndrome both clinically and at the molecular level allows genotype-phenotype correlations that provide clues to help elucidate the clinical implications.

SUBMITTER: Ochando I

PROVIDER: S-EPMC3681196 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Clinical and molecular characterization of a patient with a combination of a deletion and a duplication of 22q13 using array CGH.

Ochando Isabel I Urbano Antonio A Rubio Juana J Rueda Joaquín J

The application of clinical genetics 20120907

Phelan-McDermid syndrome is caused by the loss of terminal regions of different sizes at 22q13. There is a wide range of severity of symptoms in patients with a 22q13 deletion, but these patients usually show neonatal hypotonia, global developmental delay, and dysmorphic traits. We carried out a clinical and molecular characterization of a patient with neonatal hypotonia and dysmorphic features. Array-based comparative genomic hybridization showed an 8.24 Mb terminal deletion associated with a 0 ...[more]

PMID: 23776384

Similar Datasets

22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.

Project description:The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype-phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of 13 patients. Developmental delay and speech abnormalities were common to all and comparable in frequency and severity to previously reported cases. Array-based comparative genomic hybridization showed the deletions to vary from 95 kb to 8.5 Mb. We also carried out high-resolution 244K array comparative genomic hybridization in 10 of 13 patients, that defined the proximal and distal breakpoints of each deletion and helped determine the size, extent, and gene content within the deletion. Two patients had a smaller 95 kb terminal deletion with breakpoints within the SHANK3 gene while three other patients had a similar 5.5 Mb deletion implying the recurrent nature of these deletions. The two largest deletions were found in patients with ring chromosome 22. No correlation could be made with deletion size and phenotype although complete/partial SHANK3 was deleted in all patients. There are very few reports on array comparative genomic hybridization analysis on patients with the 22q13.3 deletion syndrome, and we aim to accurately characterize these patients both clinically and at the molecular level, to pave the way for further genotype-phenotype correlations. (c) 2010 Wiley-Liss, Inc.

| S-EPMC3119894 | biostudies-literature

Molecular characterization of CPS1 deletions by array CGH.

Project description:CPSI deficiency usually results in severe hyperammonemia presenting in the first days of life warranting prompt diagnosis. Most CPS1 defects are non-recurrent, private mutations, including point mutation, small insertions and deletions. In this study, we report the detection of large deletions varying from 1.4 kb to >130 kb in the CPS1 gene of 4 unrelated patients by targeted array CGH. These results underscore the importance of analysis of large deletions when only one mutation or no mutations are identified in cases where CPSI deficiency is strongly indicated.

| S-EPMC4869965 | biostudies-literature

FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male.

Project description:This study presents a 28-year-old infertile male who was referred to the cytogenetic laboratory for chromosomal analysis after 4 years of regular unprotected intercourse in whom non-obstructive azoospermia was revealed. Standard cytogenetic G-banding was performed on metaphase spreads and a de-novo karyotype 46,X,der(Y)(q11.22;p11.3) was identified. This analysis was followed by flourescence in-situ hybridization(FISH) and array comparative genomic hybridization (aCGH). Finally, the patient's karyotype was identified as 46,X,der(Y)(qter→q11.221::p11.31→qter).ish der(Y) (qter+,pter-,SHOX+,SRY+,Ycen+,DYZ3+;DYZ1+,qter+).arrYq11.221q12(14,448,863-59,288,511) x2, Yp11.32p11.31(104,062-266,388) x0. It is proposed that de-novo derivative monocentric Y chromosome with duplicated region Y qter→q11.221::p11.31→qter with partial deletion of Yp PAR1 region most probably can perturb the conjugation of sex chromosomes during first meiotic division of spermatogenic arrested differentiation (development).

| S-EPMC4758203 | biostudies-literature

Combined 22q11.1-q11.21 deletion with 15q11.2-q13.3 duplication identified by array-CGH in a 6 years old boy.

Project description:BACKGROUND:Deletions of chromosome 22q11 are present in over 90% of cases of DiGeorge or Velo-Cardio-Facial syndrome (DGS/VCFS). 15q11-q13 duplication is another recognized syndrome due to rearrangements of several genes, belonging to the category of imprinted genes. The phenotype of this syndrome varies but has been clearly associated with developmental delay and autistic spectrum disorders. Co-existence of the two syndromes has not been reported so far. RESULTS:Here we report a 6-year-old boy presenting growth retardation, dysmorphic features and who exhibited learning difficulties. Fluorescence in situ hybridization (FISH) analysis of the proband revealed a deletion of DiGeorge Syndrome critical region (TUPLE). Array-CGH analysis revealed an interstitial duplication of 12 Mb in size in the area 15q11.2-q13.3, combined with a 3.2 Mb deletion at region 22q11.1-q11.21. FISH analysis in the mother showed a cryptic balanced translocation between chromosome 15 and chromosome 22 (not evident by classic karyotyping). DISCUSION: The clinical manifestations could be related to both syndromes and the importance of array-CGH analysis in cases of unexplained developmental delay is emphasized. The present case further demonstrates how molecular cytogenetic techniques applied in the parents were necessary for the genetic counseling of the family.

| S-EPMC3058102 | biostudies-literature

Clinical and molecular findings in nine new cases of tetrasomy 18p syndrome: FISH and array CGH characterization.

Project description:Background:Small Supernumerary Marker Chromosomes (sSMC) are rare chromosomal abnormalities, which have abnormal banding arrangement and take many shapes. Several disorders have been correlated with sSMC presence. The aim of this study is to characterize the sSMC derived from chromosome 18 by Fluorescence in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH). Results:Nine children with dysmorphic features have been investigated. They have these features in common: a triangular face, low-set ears, a large mouth with a thin upper lip, and a horizontal palpebral fissure. Epicanthus and strabismus were present in two patients. In addition, we have noticed microcephaly and mental and/or developmental delay with low birth weight. However, two patients had standard birth weight; one patient had hypospadias; two had skin problems; and three showed different congenital heart defects. One patient had corpus callosum hypoplasia. Systematic karyotype analysis revealed a de novo supernumerary chromosome. Array CGH showed a gain in copy number on the short arm of chromosome 18 in the nine cases. In one case, the sSMC seemed to be in mosaic. The breakpoints of the marker were identified using aCGH and FISH. Thus, the sSMC led to 18p tetrasomy with approximately 14?Mb lengths, between 364344 and 14763575 based on the human genome version 18. Conclusions:These results have been completed by FISH in order to ascertain the shape of the sSMC. Our results confirm the uniqueness and particularity of the iso18p syndrome on the phenotypic as well as on the genetic level.

| S-EPMC6368812 | biostudies-literature

Clinical and molecular characterization of a patient with interstitial 6q21q22.1 deletion.

Project description:BackgroundInterstitial 6q deletions, involving the 6q15q25 chromosomal region, are rare events characterized by variable phenotypes and no clear karyotype/phenotype correlation has been determined yet.ResultsWe present a child with a 6q21q22.1 deletion, characterized by array-CGH, associated with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, skeletal, muscle, and brain anomalies.DiscussionIn our patient, the 6q21q22.1 deleted region contains ten genes (TRAF3IP2, FYN, WISP3, TUBE1, LAMA4, MARCKS, HDAC2, HS3ST5, FRK, COL10A1) and two desert gene regions. We discuss here if these genes had some role in determining the phenotype of our patient in order to establish a possible karyotype/phenotype correlation.

| S-EPMC4457201 | biostudies-literature

Reliable single cell array CGH for clinical samples.

Project description:BackgroundDisseminated cancer cells (DCCs) and circulating tumor cells (CTCs) are extremely rare, but comprise the precursors cells of distant metastases or therapy resistant cells. The detailed molecular analysis of these cells may help to identify key events of cancer cell dissemination, metastatic colony formation and systemic therapy escape.Methodology/principal findingsUsing the Ampli1™ whole genome amplification (WGA) technology and high-resolution oligonucleotide aCGH microarrays we optimized conditions for the analysis of structural copy number changes. The protocol presented here enables reliable detection of numerical genomic alterations as small as 0.1 Mb in a single cell. Analysis of single cells from well-characterized cell lines and single normal cells confirmed the stringent quantitative nature of the amplification and hybridization protocol. Importantly, fixation and staining procedures used to detect DCCs showed no significant impact on the outcome of the analysis, proving the clinical usability of our method. In a proof-of-principle study we tracked the chromosomal changes of single DCCs over a full course of high-dose chemotherapy treatment by isolating and analyzing DCCs of an individual breast cancer patient at four different time points.Conclusions/significanceThe protocol enables detailed genome analysis of DCCs and thereby assessment of the clonal evolution during the natural course of the disease and under selection pressures. The results from an exemplary patient provide evidence that DCCs surviving selective therapeutic conditions may be recruited from a pool of genomically less advanced cells, which display a stable subset of specific genomic alterations.

| S-EPMC3897541 | biostudies-literature

High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage.

Project description:Maternally derived duplication of the imprinted region of chromosome 15q11-q14 leads to a complex neurobehavioral phenotype that often includes autism, cognitive deficits, and seizures. Multiple repeat elements within the region mediate a variety of rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi and Angelman syndromes. To elucidate the molecular structure of these duplication chromosomes, we designed a high-resolution array comparative genomic hybridization (array CGH) platform. The array contains 79 clones that form a gapped contig across the critical region on chromosome 15q11-q14 and 21 control clones from other autosomes and the sex chromosomes. We used this array to examine a set of 48 samples from patients with segmental aneuploidy of chromosome 15q. Using the array, we were able to determine accurately the dosage, which ranged from 1 to 6 copies, and also to detect atypical and asymmetric rearrangements. In addition, the increased resolution of the array allowed us to position two previously reported breakpoints within the contig. These results indicate that array CGH is a powerful technique to study rearrangements of proximal chromosome 15q.

| S-EPMC1216061 | biostudies-literature

Prolidase Deficiency in a Mexican-American Patient Identified by Array CGH Reveals a Novel and the Largest PEPD Gene Deletion.

Project description:Prolidase deficiency (PD) is a rare genetic disorder caused by mutations in the peptidase D (PEPD) gene, affecting collagen degradation. Features include lower extremity ulcers, facial dysmorphism, frequent respiratory infections, and intellectual disability, though there is significant intra- and interfamilial variability. Twenty-eight mutations have been previously reported, all either small deletions/duplications or point mutations discovered by enzyme or DNA assays. PD has been reported in patients of various ethnic backgrounds, but never in the Mexican-American population. We describe the first Mexican-American patient with PD, who presented with typical facial features, developmental delay, microcephaly, and xerosis. Chromosome microarray analysis (CMA) revealed a homozygous deletion in the region of 19q13.11, estimated to be between 124.79 and 195.72 kb in size, representing the largest PEPD gene deletion reported to date and the first discovered by CMA.

| S-EPMC4906423 | biostudies-literature

Cytogenetic and Array-CGH Characterization of a Simple Case of Reciprocal t(3;10) Translocation Reveals a Hidden Deletion at 5q12.

Project description:Chromosome deletions, including band 5q12, have rarely been reported and have been associated with a wide range of clinical manifestations, such as postnatal growth retardation, intellectual disability, hyperactivity, nonspecific ocular defects, facial dysmorphism, and epilepsy. In this study, we describe for the first time a child with growth retardation in which we identified a balanced t(3;10) translocation by conventional cytogenetic analysis in addition to an 8.6 Mb 5q12 deletion through array-CGH. Our results show that the phenotypic abnormalities of a case that had been interpreted as "balanced" by conventional cytogenetics are mainly due to a cryptic deletion, highlighting the need for molecular investigation in subjects with an abnormal phenotype before assuming the cause is an apparently simple cytogenetic rearrangement. Finally, we identify PDE4D and PIK3R1 genes as the two major candidates responsible for the clinical features expressed in our patient.

| S-EPMC8226940 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data