Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays

Hoyer, Juliane; Dreweke, Alexander; Becker, Christian; Göhring, Ina; Thiel, Christian T.; Peippo, Maarit; Rauch, Ralf; Hofbeck, Michael; Trautmann, Udo; Zweier, Christiane; Zenker, Martin; Hüffmeier, Ulrike; Kraus, Cornelia; Ekici, Arif B.; Rüschendorf, Franz; Nürnberg, Peter; Reis, André; Rauch, Anita

doi:10.1136/jmg.2007.050914

Cited by 75 publications

(54 citation statements)

References 34 publications

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“…The yield of different diagnostic approaches is dependent on patient ascertainment, although the influence of patient selection on the detection rate might be smaller than previously thought. 22 In the five European studies summarised above, the 1 Mb array-CGH diagnostic detection rates varied from 8% 10 to 16%. 23 Of note, some of the patients in these studies had been pre-screened for subtelomeric imbalances, and elimination of these ten patients from our cohort would have reduced our diagnostic detection rate to 5.4%.…”

Section: Discussionmentioning

confidence: 99%

Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development

et al. 2008

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During a 6-year period, 590 patients suspected of having a minor or cryptic genomic imbalance as the cause of mental retardation with dysmorphic signs þ /À malformations have been investigated with highresolution comparative genomic hybridisation (HR-CGH) in our diagnostic laboratory. Thirty-six patients had a small chromosomal aberration detected by routine karyotyping, and 554 patients had a normal G-banded karyotype. In the latter group, a genomic imbalance was detected by HR-CGH in 40 patients (7.2%): 29 deletions, 3 duplications, 4 unbalanced translocations, and 4 occult trisomy mosaicisms. When microarray-based comparative genomic hybridisation (array-CGH) became available, all HR-CGH-positive samples were also investigated by 1 Mb resolution array-CGH for more precise mapping. From the 514 patients with normal HR-CGH findings, a subset of 20 patients with particularly high suspicion of having a chromosomal imbalance was selected for array-CGH. In four of them (20%), an imbalance was detected: three deletions and one duplication. Of note, 73 out of the 80 array-CGH mapped patients had a de novo chromosomal rearrangement (91%). Taken together, this work provides phenotype -genotype information on 80 patients with minor and cryptic chromosomal imbalances.

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Section: Discussionmentioning

confidence: 99%

Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development

et al. 2008

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“…3 This patient was mentioned within a larger series previously ( 3 patient 77). The deletion was confirmed by twocolour FISH with locus-specific probe RP11-88D22 and a subtelomeric control probe on lymphocyte metaphase spreads of the patient and her parents as described previously.…”

Section: Patientmentioning

confidence: 72%

“…The deletion was confirmed by twocolour FISH with locus-specific probe RP11-88D22 and a subtelomeric control probe on lymphocyte metaphase spreads of the patient and her parents as described previously. 3 Patient 2 BAC array analysis using the Sanger 1 Mb array was performed as previously described. 17 FISH was performed with multiple tile path RPCI11 clones obtained from BAC PAC resources (http://bacpac.chori.org) directly labelled with either Vysis Spectrum Orange-dUTP or Spectrum Green-dUTP (Vysis) as previously described 17 to size the deletion in the proband and to screen the parents.…”

Section: Patientmentioning

confidence: 99%

A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

et al. 2009

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Molecular karyotyping is being increasingly applied to delineate novel disease causing microaberrations and related syndromes in patients with mental retardation of unknown aetiology. We report on three unrelated patients with overlapping de novo interstitial microdeletions involving 5q14.3-q15. All three patients presented with severe psychomotor retardation, epilepsy or febrile seizures, muscular hypotonia and variable brain and minor anomalies. Molecular karyotyping revealed three overlapping microdeletions measuring 5.7, 3.9 and 3.6 Mb, respectively. The microdeletions were identified using single nucleotide polymorphism (SNP) arrays (Affymetrix 100K and Illumina 550K) and array comparative genomic hybridization (1 Mb Sanger array-CGH). Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative PCR. All three aberrations were confirmed and proven to have occurred de novo. The boundaries and sizes of the deletions in the three patients were different, but an overlapping region of around 1.6 Mb in 5q14.3 was defined. It included five genes: CETN3, AC093510.2, POLR3G, LYSMD3 and the proximal part of GPR98/MASS1, a known epilepsy gene. Haploinsufficiency of GPR98/MASS1 is probably responsible for the seizure phenotype in our patients. At least one other gene contained in the commonly deleted region, LYSMD3, shows a high level of central nervous expression during embryogenesis and is also, therefore, a good candidate gene for other central nervous system (CNS) symptoms, such as psychomotor retardation, brain anomalies and muscular hypotonia of the 5q14.3 microdeletion syndrome.

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“…The copy number change (or copy number variant [CNV]) may include deletions, duplications, or amplifications at any locus, as long as that region is represented on the array. CMA, independent of whether it is "whole genome" or "targeted" and what type of DNA substrate (single-nucleotide polymorphisms, 31 oligonucleotides, complementary DNAs, or bacterial artificial chromosomes), 32 identifies deletions and/or duplications of chromosome material with a high degree of sensitivity in a more efficient manner than FISH techniques. Two main factors define the resolution of CMA: (1) the size of the nucleic acid targets; and (2) the density of coverage over the genome.…”

Section: Diagnosismentioning

confidence: 99%

Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays

Moeschler¹,

Shevell²,

Saul³

et al. 2014

Pediatrics

436

420

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Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed.

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Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays

Cited by 75 publications

References 34 publications

Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development

Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development

A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays

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