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Based Comparative Genome Hybridization in Clinical Genetics
Humanitarian Fund.
Top of pageAbstractAbnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array based comparative genomic hybridization (array CGH) is a high resolution, whole genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2 q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false positive rate of 0.2% was calculated for clone by clone analysis, whereas the per patient false positive rate was 20%. Standard cytogenetic techniques, such as G banding fake cartier gold diamond ring and SKY cartier fake men wedding ring (spectral karyotyping), can identify large aberrations including deletions, duplications, amplifications and unbalanced translocations, although their limited resolution makes these tools unreliable for the detection of copy number changes of less than 5 Mb (2). FISH has the advantage of high resolution, but is best suited for the confirmation of known microdeletion and microduplication syndromes in patients presenting with a suggestive phenotype due to the limited number of chromosomal loci that can be simultaneously analyzed.
Array CGH is an innovative high resolution technology that detects and maps submicroscopic DNA copy number alterations (3,4), improving the diagnostic detection rate of subtle copy number changes. Array CGH detects quantitative aberrations spanning small regions of the genome, with resolution determined by both the size and the spacing of the clones on the array. CGH arrays have successfully identified submicroscopic unbalanced chromosomal rearrangements in multiple clinical samples. In three previous studies of patients with mental retardation and dysmorphisms that had normal karyotypes in standard cytogenetic analyses, genomewide arrays have reported rearrangement detection rates of 15%, 24%, and 10%, respectively (1,2,5). Thus, an even higher frequency of rearrangements is expected in the entire population of patients with mental retardation and dysmorphisms.
Top of pageMETHODSPatients and chromosomal analysis. All cases were referred for consultation to The Genetic Institute, Tel Aviv Sourasky Medical Center and are presented in Table 1. Patients' informed consents were obtained. Cytogenetic analysis was made according to a standard technique. Karyotypes were established according to the 1995 International System for Human Cytogenetic Nomenclature (17).
FISH analysis. Commercially available probes were used for FISH analyses of the telomeric regions at chromosomes 1q, 2q, and 12q (TelVysion, Abbot Vysis, Chicago, IL), 10q (QBiogene, Illkirch Cedex, France) and 14q (Cytocell, Windsor, CT). Commercially available probes (LSID15S11, SNRPN, GABRB3 and LSID15S10/UBE3A) for the PWS region at 15q11.2 q13, TUPLE1 and N25 for the VCF/DiGeorge region at 22q11.2 (Cytocell and Abbot Vysis, respectively), and LSILIS1 for the Miller Dieker/Lissencephaly region (Abbot Vysis) were also used for FISH analyses. The following BAC (bacterial artifical chromosome) clones that contain specific gene sequences were used as templates for FISH probes synthesis (Table 2): RPCI11 894C9 for RASSF1 (3q21.3) (M. Rocchi, University of Bari, Bari, Italy), RPCI1 74J1 for WT1 and RPCI11 307I15 for PAX6 (both at 11p13) (CHORI BACPAC Resources, Oakland, California). Cosmid 1p3 for the FLI1 gene at 11q24 (18) was provided by Dr. Shai Izraeli, and the FISH analysis for the WT1 and PAX6 genes (19) was performed using cosmids B2.1 and AN2, respectively (Dr. Karen Gronskov, personal communication). DNA probes cartier gold diamond ring imitation were directly labeled by nick translation with Spectrum Orange fluorescent nucleotide (Abbot Vysis) and coprecipitated in the presence of Cot 1 (Abbot Vysis) and salmon sperm DNA (Sigma Chemical Co. Aldrich, Rehovot, Israel). The chromosome preparation and the fluorescent probes were denatured separately at 73 and probes were allowed to preanneal at 37 before overnight hybridization. Following posthybridization washes, the chromosomes were counterstained with 4 (DAPI Vectashield, Vector Laboratories, Burlingame, CA). Hybridization signals were detected using rhodamine and DAPI filters on an Olympus B52 microscope, and the images were captured using a CCD camera and Cytovision Software (Applied Imaging, Santa Clara, CA). For the RASSF1 gene (3q21.3), in addition to FISH hybridization with the entire BAC as a probe, three specific genomic fragments of about 6 Kb each, representing the 5 the middle, and the 3 regions of the gene, were prepared by polymerase chain reaction (PCR), pooled together and labeled for FISH as described. The primers for the specific RASSF1 FISH probes and the PCR conditions are available upon request.
Array CGH. High molecular weight genomic DNA was extracted from patient's peripheral blood leukocytes using the PureGene DNA Isolation Kit (Gentra Systems, Minneapolis, MN) according to the manufacturer's instructions. Detection of gene copy number was performed by array CGH using Abbot Vysis GenoSensor system (Abbot Vysis) according to the manufacturer's instructions (Abbot Vysis). Briefly, 100 ng of each test DNA and normal reference DNA (from an individual of the opposite sex of the test sample) was labeled by Random Priming Kit (Abbot Vysis) to incorporate Cy3 or Cy5 fluorophores (Perkin Elmer, Boston, MA). DNA was denatured at 100 for 10 min and was cooled to 4 before the addition of Klenow fragments and nucleotide mix. After incubation at 37 for 2 h, the samples were digested using a 1:20 DNAse dilution for 1 h at 15 Unincorporated nucleotides were then removed using Sephadex G 50 spin columns (Amersham Biosciences, Piscataway, NJ). Probes were precipitated with ethanol and resuspended in 10 mmol/L Tris, pH 8.0. Equal aliquots of labeled test and reference DNA were combined in a tube with hybridization buffer, denatured at 80 for 10 min, and incubated for 1 h at 37 to allow blocking of repetitive sequences. The solutions were then hybridized for 72 h at 37 with a GenoSensor Array 300. This array contains 287 genomic clones, including those for each human telomere, as well as all the known microdeletion syndromes and additional selected loci representing each chromosome arm. After hybridization, the arrays were washed in 50% formamide/2 SSC at 40 and 1 SSC at 25 and were counterstained with 4 (DAPI). Hybridization signal images in three colors (Cy3, Cy5, and DAPI blue) were then analyzed by the GenoSensor reader system based on DAPI staining that identified target spots and their location on the grid. By analyzing the set of Cy3/Cy5 ratios (test to reference ratios) on all targets, the GenoSensor Array 300 Reader Software (version 1) calculates the ratio most representative of the modal DNA copy number of the sample DNA. For each target the normalized ratio, relative to the modal DNA copy number is calculated. This normalized ratio of the target indicates the degree of gain or loss of copy number, and for each clone the copy number changes are presented. For each target, a p value is calculated automatically by the GenoSensor Array 300 Reader Software (Abbot Vysis), and a p value of was considered significant.
Top of pageRESULTSWe screened eight patients with mental deficiency, multiple congenital anomalies, and dysmorphic features for submicroscopic chromosomal imbalances using array CGH. All cases were analyzed previously by routine cytogenetic techniques, and chromosomal aberrations were identified in three. CGH results were compared with previous G banding and FISH analyses to ascertain whether CGH arrays could verify previously detected abnormalities. In the remaining five cases, array CGH was implemented in an attempt to identify potential submicroscopic rearrangements in complex undiagnosed patients. Each analysis was performed once by an operator with no knowledge of the previous diagnosis. We also performed four versus normal control experiments and confirmed these threshold values. Our analysis of the normal control samples resulted in a standard deviation (SD) of 0.05, suggesting that 4 SDs determine the threshold of either gains or losses. Power analysis, assuming an SD of 0.05 among samples and a mean difference of 0.2 between the normal controls and the patients was 0.996 when n 4 in each group (Power and Precision Software, Biostat, Englewood, NJ). Gains and/or loss of chromosomal material were detected in six of the eight patients tested (Table 2).
Validation experiments. In two of the three previously diagnosed patients (cases 1 and 2), array CGH validated the results of FISH and G banding. In case 1, we verified unbalanced t(2;12)(q37;q24) with trisomy 12q37 and monosomy of 2q24 In case 2, we validated the trisomy of 1qtel and the adjacent AKT gene (at 1q44), and the deletion of 11qtel. The latter is compatible with the balanced translocation t (1;11)(q42;q23) detected in this family.
FISH analysis of case 3 using cosmid probes detected the deletion of one copy of the PAX6 and WT1 genes located at chromosome 11p13 (22). PAX6 gene is not present on the Array 300, but a T/R ratio of 0.81 and a significant p value of 0.002 were observed for WT1 in the Array 300 analysis of this case (Fig. 1A). Although a few other probes came close to a T/R ratio of 0.8 (0.81 none of them, except the WT1 probe in case 3, had a significant p value. Therefore, this target was designated as a borderline false negative. Repeated FISH analysis of case 3 with BAC probes for PAX6 and WT1 genes validated the deletion of one copy of the PAX6 gene, but detected two copies of the WT1 gene (Fig. 1B and C, respectively), suggesting that the differences in probes' sizes (BAC versus cosmid) determine whether the deletion could unequivocally be detected. (A) The array CGH profile. The WT1 targets are marked in a yellow frame. Because the T/R ratio is 0.81, the signal is gray and does not appear as a deletion. Male test DNA was hybridized against female reference DNA, resulting in deletion signals of X chromosome targets (red) and amplification signals of Y chromosome targets (green). (B) FISH analysis using PAX6 RPCI11 307I15 BAC clone as probe. The red arrow indicates the deletion. (C) FISH analysis using WT1 RPCI1 74J1 BAC clone as probe.
Full figure and legend (363K)
Detection of novel chromosomal aberrations in complex undiagnosed patients. CGH microarray results provided diagnoses in two of the five previously undiagnosed cases. In case 4, array CGH analysis showed losses of one copy of two probes in the 15q11.2 q13 region: SNRPN and GABRB3. Four target probes were tested at the Prader Willi/Angelman region, D15S11 SNRPN, UBE3A and GABRB3, from the centromere to the telomere, using FISH probes and the Array 300. The probes located at both ends of this region, GABRB3 and D15S11, demonstrated one and two copies of these genes, respectively, using both methods. With the two other probes, there was a discrepancy between the FISH and Array 300 results. Deletion of one UBE3A copy was seen in FISH analysis, but not in the array CGH. In contrast, deletion of one SNRPN copy was detected in the Array 300 analysis, whereas FISH analysis demonstrated two copies, although one signal was weak, suggesting that one of the breakpoints might have occurred within the SNRPN gene region. Because hypopigmentation was found in this patient, we further suggest that the second deletion breakpoint located distal to the P locus. Additional microdeletion of one of the subtelomeric clones at the 14qtel was not validated by the FISH analysis.
Case 5 demonstrated contiguous microdeletion of three genes at the 22q11.2 region: GSCL, HIRA, and TBX1. Additional microdeletion of one of the subtelomeric clones at the 10qtel was not detected by FISH analysis.
In case 6, FISH hybridizations using probes of both the entire BAC and specific sequences of this gene did not confirm the deletion of RASSF1 at 3q21.3 detected by the Array 300, and it was therefore regarded as false positive.
Finally, no abnormalities were detected in the array CGH analyses of cases 7 and 8.
Top of pageDISCUSSIONWe used array CGH as an additional tool to resolve undiagnosed complex cases of children with mental deficiency, multiple malformations, and dysmorphic features. The GenoSensor Array 300 chip, containing 287 different probes representing regions significant in cytogenetics or oncology, successfully identified gains and/or losses of DNA copies in cartier diamond replica rings five of the eight cases examined.
Results from our array CGH analyses of cases 1 and 2 correlated well with the rearrangements previously detected by FISH. The array CGH analysis also detected chromosomal alterations in two previously undiagnosed cases (cases 4 and 5). Microdeletion at the chromosome 15q11 q12 region was detected in case 4, confirming the suspected clinical diagnosis of Prader Willi syndrome in the newborn boy. The discrepancies between the Array 300 results and the commercial FISH probe analysis emphasize the importance of specific FISH probes for the validation of microarray data.in concern of cartier bracelet pink gold screw imitation Latest mode magazine present tell you
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Humanitarian Fund.
Top of pageAbstractAbnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array based comparative genomic hybridization (array CGH) is a high resolution, whole genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2 q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false positive rate of 0.2% was calculated for clone by clone analysis, whereas the per patient false positive rate was 20%. Standard cytogenetic techniques, such as G banding fake cartier gold diamond ring and SKY cartier fake men wedding ring (spectral karyotyping), can identify large aberrations including deletions, duplications, amplifications and unbalanced translocations, although their limited resolution makes these tools unreliable for the detection of copy number changes of less than 5 Mb (2). FISH has the advantage of high resolution, but is best suited for the confirmation of known microdeletion and microduplication syndromes in patients presenting with a suggestive phenotype due to the limited number of chromosomal loci that can be simultaneously analyzed.
Array CGH is an innovative high resolution technology that detects and maps submicroscopic DNA copy number alterations (3,4), improving the diagnostic detection rate of subtle copy number changes. Array CGH detects quantitative aberrations spanning small regions of the genome, with resolution determined by both the size and the spacing of the clones on the array. CGH arrays have successfully identified submicroscopic unbalanced chromosomal rearrangements in multiple clinical samples. In three previous studies of patients with mental retardation and dysmorphisms that had normal karyotypes in standard cytogenetic analyses, genomewide arrays have reported rearrangement detection rates of 15%, 24%, and 10%, respectively (1,2,5). Thus, an even higher frequency of rearrangements is expected in the entire population of patients with mental retardation and dysmorphisms.
Top of pageMETHODSPatients and chromosomal analysis. All cases were referred for consultation to The Genetic Institute, Tel Aviv Sourasky Medical Center and are presented in Table 1. Patients' informed consents were obtained. Cytogenetic analysis was made according to a standard technique. Karyotypes were established according to the 1995 International System for Human Cytogenetic Nomenclature (17).
FISH analysis. Commercially available probes were used for FISH analyses of the telomeric regions at chromosomes 1q, 2q, and 12q (TelVysion, Abbot Vysis, Chicago, IL), 10q (QBiogene, Illkirch Cedex, France) and 14q (Cytocell, Windsor, CT). Commercially available probes (LSID15S11, SNRPN, GABRB3 and LSID15S10/UBE3A) for the PWS region at 15q11.2 q13, TUPLE1 and N25 for the VCF/DiGeorge region at 22q11.2 (Cytocell and Abbot Vysis, respectively), and LSILIS1 for the Miller Dieker/Lissencephaly region (Abbot Vysis) were also used for FISH analyses. The following BAC (bacterial artifical chromosome) clones that contain specific gene sequences were used as templates for FISH probes synthesis (Table 2): RPCI11 894C9 for RASSF1 (3q21.3) (M. Rocchi, University of Bari, Bari, Italy), RPCI1 74J1 for WT1 and RPCI11 307I15 for PAX6 (both at 11p13) (CHORI BACPAC Resources, Oakland, California). Cosmid 1p3 for the FLI1 gene at 11q24 (18) was provided by Dr. Shai Izraeli, and the FISH analysis for the WT1 and PAX6 genes (19) was performed using cosmids B2.1 and AN2, respectively (Dr. Karen Gronskov, personal communication). DNA probes cartier gold diamond ring imitation were directly labeled by nick translation with Spectrum Orange fluorescent nucleotide (Abbot Vysis) and coprecipitated in the presence of Cot 1 (Abbot Vysis) and salmon sperm DNA (Sigma Chemical Co. Aldrich, Rehovot, Israel). The chromosome preparation and the fluorescent probes were denatured separately at 73 and probes were allowed to preanneal at 37 before overnight hybridization. Following posthybridization washes, the chromosomes were counterstained with 4 (DAPI Vectashield, Vector Laboratories, Burlingame, CA). Hybridization signals were detected using rhodamine and DAPI filters on an Olympus B52 microscope, and the images were captured using a CCD camera and Cytovision Software (Applied Imaging, Santa Clara, CA). For the RASSF1 gene (3q21.3), in addition to FISH hybridization with the entire BAC as a probe, three specific genomic fragments of about 6 Kb each, representing the 5 the middle, and the 3 regions of the gene, were prepared by polymerase chain reaction (PCR), pooled together and labeled for FISH as described. The primers for the specific RASSF1 FISH probes and the PCR conditions are available upon request.
Array CGH. High molecular weight genomic DNA was extracted from patient's peripheral blood leukocytes using the PureGene DNA Isolation Kit (Gentra Systems, Minneapolis, MN) according to the manufacturer's instructions. Detection of gene copy number was performed by array CGH using Abbot Vysis GenoSensor system (Abbot Vysis) according to the manufacturer's instructions (Abbot Vysis). Briefly, 100 ng of each test DNA and normal reference DNA (from an individual of the opposite sex of the test sample) was labeled by Random Priming Kit (Abbot Vysis) to incorporate Cy3 or Cy5 fluorophores (Perkin Elmer, Boston, MA). DNA was denatured at 100 for 10 min and was cooled to 4 before the addition of Klenow fragments and nucleotide mix. After incubation at 37 for 2 h, the samples were digested using a 1:20 DNAse dilution for 1 h at 15 Unincorporated nucleotides were then removed using Sephadex G 50 spin columns (Amersham Biosciences, Piscataway, NJ). Probes were precipitated with ethanol and resuspended in 10 mmol/L Tris, pH 8.0. Equal aliquots of labeled test and reference DNA were combined in a tube with hybridization buffer, denatured at 80 for 10 min, and incubated for 1 h at 37 to allow blocking of repetitive sequences. The solutions were then hybridized for 72 h at 37 with a GenoSensor Array 300. This array contains 287 genomic clones, including those for each human telomere, as well as all the known microdeletion syndromes and additional selected loci representing each chromosome arm. After hybridization, the arrays were washed in 50% formamide/2 SSC at 40 and 1 SSC at 25 and were counterstained with 4 (DAPI). Hybridization signal images in three colors (Cy3, Cy5, and DAPI blue) were then analyzed by the GenoSensor reader system based on DAPI staining that identified target spots and their location on the grid. By analyzing the set of Cy3/Cy5 ratios (test to reference ratios) on all targets, the GenoSensor Array 300 Reader Software (version 1) calculates the ratio most representative of the modal DNA copy number of the sample DNA. For each target the normalized ratio, relative to the modal DNA copy number is calculated. This normalized ratio of the target indicates the degree of gain or loss of copy number, and for each clone the copy number changes are presented. For each target, a p value is calculated automatically by the GenoSensor Array 300 Reader Software (Abbot Vysis), and a p value of was considered significant.
Top of pageRESULTSWe screened eight patients with mental deficiency, multiple congenital anomalies, and dysmorphic features for submicroscopic chromosomal imbalances using array CGH. All cases were analyzed previously by routine cytogenetic techniques, and chromosomal aberrations were identified in three. CGH results were compared with previous G banding and FISH analyses to ascertain whether CGH arrays could verify previously detected abnormalities. In the remaining five cases, array CGH was implemented in an attempt to identify potential submicroscopic rearrangements in complex undiagnosed patients. Each analysis was performed once by an operator with no knowledge of the previous diagnosis. We also performed four versus normal control experiments and confirmed these threshold values. Our analysis of the normal control samples resulted in a standard deviation (SD) of 0.05, suggesting that 4 SDs determine the threshold of either gains or losses. Power analysis, assuming an SD of 0.05 among samples and a mean difference of 0.2 between the normal controls and the patients was 0.996 when n 4 in each group (Power and Precision Software, Biostat, Englewood, NJ). Gains and/or loss of chromosomal material were detected in six of the eight patients tested (Table 2).
Validation experiments. In two of the three previously diagnosed patients (cases 1 and 2), array CGH validated the results of FISH and G banding. In case 1, we verified unbalanced t(2;12)(q37;q24) with trisomy 12q37 and monosomy of 2q24 In case 2, we validated the trisomy of 1qtel and the adjacent AKT gene (at 1q44), and the deletion of 11qtel. The latter is compatible with the balanced translocation t (1;11)(q42;q23) detected in this family.
FISH analysis of case 3 using cosmid probes detected the deletion of one copy of the PAX6 and WT1 genes located at chromosome 11p13 (22). PAX6 gene is not present on the Array 300, but a T/R ratio of 0.81 and a significant p value of 0.002 were observed for WT1 in the Array 300 analysis of this case (Fig. 1A). Although a few other probes came close to a T/R ratio of 0.8 (0.81 none of them, except the WT1 probe in case 3, had a significant p value. Therefore, this target was designated as a borderline false negative. Repeated FISH analysis of case 3 with BAC probes for PAX6 and WT1 genes validated the deletion of one copy of the PAX6 gene, but detected two copies of the WT1 gene (Fig. 1B and C, respectively), suggesting that the differences in probes' sizes (BAC versus cosmid) determine whether the deletion could unequivocally be detected. (A) The array CGH profile. The WT1 targets are marked in a yellow frame. Because the T/R ratio is 0.81, the signal is gray and does not appear as a deletion. Male test DNA was hybridized against female reference DNA, resulting in deletion signals of X chromosome targets (red) and amplification signals of Y chromosome targets (green). (B) FISH analysis using PAX6 RPCI11 307I15 BAC clone as probe. The red arrow indicates the deletion. (C) FISH analysis using WT1 RPCI1 74J1 BAC clone as probe.
Full figure and legend (363K)
Detection of novel chromosomal aberrations in complex undiagnosed patients. CGH microarray results provided diagnoses in two of the five previously undiagnosed cases. In case 4, array CGH analysis showed losses of one copy of two probes in the 15q11.2 q13 region: SNRPN and GABRB3. Four target probes were tested at the Prader Willi/Angelman region, D15S11 SNRPN, UBE3A and GABRB3, from the centromere to the telomere, using FISH probes and the Array 300. The probes located at both ends of this region, GABRB3 and D15S11, demonstrated one and two copies of these genes, respectively, using both methods. With the two other probes, there was a discrepancy between the FISH and Array 300 results. Deletion of one UBE3A copy was seen in FISH analysis, but not in the array CGH. In contrast, deletion of one SNRPN copy was detected in the Array 300 analysis, whereas FISH analysis demonstrated two copies, although one signal was weak, suggesting that one of the breakpoints might have occurred within the SNRPN gene region. Because hypopigmentation was found in this patient, we further suggest that the second deletion breakpoint located distal to the P locus. Additional microdeletion of one of the subtelomeric clones at the 14qtel was not validated by the FISH analysis.
Case 5 demonstrated contiguous microdeletion of three genes at the 22q11.2 region: GSCL, HIRA, and TBX1. Additional microdeletion of one of the subtelomeric clones at the 10qtel was not detected by FISH analysis.
In case 6, FISH hybridizations using probes of both the entire BAC and specific sequences of this gene did not confirm the deletion of RASSF1 at 3q21.3 detected by the Array 300, and it was therefore regarded as false positive.
Finally, no abnormalities were detected in the array CGH analyses of cases 7 and 8.
Top of pageDISCUSSIONWe used array CGH as an additional tool to resolve undiagnosed complex cases of children with mental deficiency, multiple malformations, and dysmorphic features. The GenoSensor Array 300 chip, containing 287 different probes representing regions significant in cytogenetics or oncology, successfully identified gains and/or losses of DNA copies in cartier diamond replica rings five of the eight cases examined.
Results from our array CGH analyses of cases 1 and 2 correlated well with the rearrangements previously detected by FISH. The array CGH analysis also detected chromosomal alterations in two previously undiagnosed cases (cases 4 and 5). Microdeletion at the chromosome 15q11 q12 region was detected in case 4, confirming the suspected clinical diagnosis of Prader Willi syndrome in the newborn boy. The discrepancies between the Array 300 results and the commercial FISH probe analysis emphasize the importance of specific FISH probes for the validation of microarray data.
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