XLMR 180K Oligo ArrayPlus
X-linked intellectual disability (XLID) and X-linked mental retardation (XLMR) are a complex collection of clinically and genetically diverse disorders stemming from variations in the X chromosome.
PrintX-linked intellectual disability (XLID) and X-linked mental retardation (XLMR) are a complex collection of clinically and genetically diverse disorders stemming from variations in the X chromosome.
Diagnosis of ID/MR is typically based on three main criteria: early onset of symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced adaptive skills. X-linked intellectual disability (ID) and mental retardation (MR) disability involves more than 200 conditions linked to >90 genes on the X chromosome.
The XLMR 180K Oligo ArrayPlus™: detects net gain(s) or loss(es) of genomic material throughout the whole genome with increased probe coverage and resolution within regions of the X chromosome known to contribute to intellectual disability/mental retardation. Aberrations of the X chromosome involving gain or loss of multiple genes is estimated to account for as much as 7.5% of families with a history of X-linked intellectual disability/mental retardation.
X-linked intellectual disability (ID) and mental retardation (MR) are a complex collection of clinically and genetically diverse disorders stemming from variations in the X chromosome.1 Diagnosis of MR is typically based on three main criteria: early onset of symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced adaptive skills. ID/MR individuals tend to struggle in areas including communication, health, interpersonal/social skills, leisure, safety, self-guidance and care, school performance, and work.2
X-linked intellectual disability (ID) and mental retardation (MR) involves more than 200 conditions linked to >90 genes on the X chromosome, affecting approximately 1/600-1/1000 males as well as a significant number of females.1, 2 Genomic imbalances are an underlying cause of intellectual disability/mental retardation which may or may not be associated with other congenital anomalies, developmental delay, autism, dysmorphism and numerous genetic syndromes. Chromosomal Microarray Analysis (CMA) via Array-based Comparative Genomic Hybridization (aCGH) is a technique that allows for high resolution genome-wide detection of unbalanced structural and numerical chromosomal abnormalities. Importantly, the level of resolution of aCGH depends only on the size and spacing of the oligonucleotide probes on the array.
The XLMR 180K Oligo ArrayPlus™ detects net gain(s) or loss(es) of genomic material th roughout the whole genome with increased probe coverage and resolution within regions of the X chromosome known to contribute to mental retardation. Aberrations of the X chromosome involving gain or loss of multiple genes is estimated to account for as much as 7.5% of families with a history of X-linked intellectual disability/mental retardation.5
The XLMR 180K Oligo ArrayPlus™ should be considered for all individuals with syndromic or non-syndromic conditions that may be caused by genomic imbalance, including dyrsmorphic features, developmental delay or mental retardation, autism spectrum disorder, birth defects or other congenital anomalies. This is especially true in families where X-linked intellectual disability/mental retardation is observed due to this array's increased probe coverage and resolution on the X chromosome. Chromosomal aberrations have been seen in 1-3% of general population with developmental delay. Aberrations of the X chromosome have been observed to account for as much as 7.5% of families with a history of X-linked intellectual disability/mental retardation. Array CGH has a much higher resolution than conventional karyotyping and many times can provide a relevant result even when the patient has an apparently normal karyotype. In addition, array CGH provides an appropriate test for patients who are candidates for multiplex or subtelomere FISH analysis. Array CGH is also clinically useful for the detection of chromosomal microdeletions/duplications in a region of interest in patients who are negative for point mutations or small intragenic aberrations.
Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified by agarose gel electrophoresis. The aCGH method is based on the hybridization of flourescently labeled patient genomic DNA (Cy-5) with flourescently labeled reference DNA (Cy-3) to a 180K oligonucleotide array. Genomic patient DNA relative to the reference DNA are represented as a flourescent ratios (Cy5/Cy3) that are further quantified by image analysis software and analytical software. Quantified results indicate each targeted-DNA sequence as loss of copy number (deletion), gain of copy number (duplication) or normal copy number. This technology has been validated using patients with known microdeletion/duplications and other unbalanced karyotypes detected by traditional cytogenetic methods. FISH analysis is performed for confirmation of aCGH results.
Analytical
Ambry’s XLMR 180K Oligo ArrayPlus™ contains 180,000 p robes, covering the 90+ X-linked intellectual disability XLID disease loci. The backbone spacing of the probes is set at an average of 10.5 kb throughout the entire human genome and at 5 kb on the X chromosome. Probe coverage and resolution is increased at all known 90+ XLID (XLMR) associated regions, but due to high GC content and homology with pseudogenes not all of the genes have complete exon coverage. The array also includes probes for the pericentromeric and subtelomeric regions with dense probe coverage spanning 10 Mb at each subtelomere.
Clinical
Chromosomal aberrations have been seen in 1-3% of general population with Developmental Delay. Aberrations of the X chromosome have been observed to account for as much as 7.5% of families with a history of X-linked intellectual disability/mental retardation.
Specimen Type: Whole Blood
Volume (per tube): 5cc EDTA purple top and 5 cc Sodium Heparin green top.
Storage Conditions: Store at room temperature or refrigerate.
Shipping Conditions: Ship via Pre-paid Ambry Chromosomal Microarray Submission Kits.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 8630 | XLMR Evaluation (CMA: 180K Oligo Array, XLMR SuperPanelTM) | 83891x1, 83892x7, 83894x23, 83898x10, 83900x1, 83901x80, 83904x80, 83909x20, 83912x2, 88384x1, 88385x1, 88386x3 |
| Technique | Days |
|---|---|
| XLMR Evaluation (CMA: 180K Oligo Array, XLMR SuperPanelTM) | 10-112 |
1 Gecz J et al. Trends in Genetics 2009;25(7):308-316.
2 Lisik M, Sieron A. Med Sci Monit. 2008;14(11):RA221-229.
3 Chiurazzi R et al. E J Hum Genet. 2008;16:422-434.
4 Fishburn J et al. Am J Med Genet. 1983;14:713-724.
5 Lugtenberg et al. J Med Genet. 2006;43:362-370.