Test Code: 4159

Chromosomal Microarray: CGH
Test Code: 4159
Turnaround time: 1 to 2 weeks

What is Chromosomal Microarray: CGH ?
This chromosomal microarray CGH test utilizes 60,000 (60K) oligonucleotides to achieve whole genome coverage at a 75 kilobase (kb) spacing. It additionally covers more than 400 targeted regions, including known recurrent microdeletion/microduplication syndromes, centromere and telomere regions and disease-causing genes. The design is based on recommendations from the International Standards for Cytogenomic Arrays (ISCA) Consortium (Bladwin et al. (2008) Genet Med 10(6):415-429).

Why Choose Chromosomal Microarray: CGH ?
When compared to conventional cytogenetic testing by G-banded chromosome analysis, this Chromosomal Microarray CGH test detects more than twice as many clinically significant imbalances. The literature supports offering whole genome chromosomal microarray testing as the first tier test for all genetic evaluations for developmental disabilities including birth defects, developmental delay, dysmorphic features, growth deficiency and intellectual disability (Miller et al. (2010) Am J Hum Genet 86(5):749-764). Testing for chromosomal imbalances by microarray is cost effective given the greater capability to detect imbalances when compared to conventional methods. This test is roughly equivalent to the cost of chromosome analysis by G-banding plus one targeted FISH study.

References
Baldwin et al. (2008) Genet Med 10(6):415-429
Miller et al. (2010) Am J Hum Genet 86(5):749-764
Manning and Hudgins (2010) Genet Med 12(11):742-745

INDICATIONS
Chromosomal microarray is indicated for the following reasons:

• Unexplained developmental delay or intellectual disability
• Autism spectrum disorders
• Epilepsy or seizures
• Dysmorphic features, congenital anomalies or birth defects
• Normal chromosome analysis and an abnormal phenotype
• Apparently balanced chromosome rearrangements and an abnormal phenotype to look for cryptic imbalances at the breakpoints
• Characterization of a previously identified chromosome abnormality

METHODOLOGY
DNA isolated from peripheral blood is hybridized to a custom array containing oligonucleotide probes across the genome to detect copy number imbalances. FISH analysis or another method, such as G-banded karyotype, is used to confirm any abnormal findings either at the time of initial testing or upon receipt of parental samples, depending on the abnormality.

DETECTION
The detection of deletions and duplications of 400 kb or greater is expected to be very high. Detection is limited to gain of copy number (duplication), loss of copy number (deletion) or normal copy number. Deletions and duplications of 400 kb or greater are reported. Smaller deletions or duplications in regions of known microdeletion/microduplication syndromes or in clinically relevant genes will also be reported. The clinical sensitivity for known microdeletion or microduplication syndromes is available in our detection rate chart. The clinical sensitivity for other disorders is dependent on the proportion of cases caused by deletions/duplications compared with other mutations not detectable by array analysis. Microarray will not detect balanced translocations, balanced inversions, imbalances smaller than the resolution of this array, point mutations or low level mosaicism (usually less than 25%) that may underlie the clinical presentation of the patient.

REFERENCE RANGE

Consecutive abnormal oligonucleotide probes are used to identify regions of imbalance. Log2 ratios less than 0.32 are indicative of a deletion or loss of genetic material, while those greater than 0.26 are indicative of a duplication or gain of genetic material.

SPECIMEN REQUIREMENTS
Additional Specimen Collection/Handling Instructions Required for this Test
If sending whole blood, both tube types are required for this test. Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) AND sodium heparin (green top) tubes: Infants (2 years): 3-5 ml in both tubes
Older Children & Adults: 7-10 ml in both tubes
Specimen Collection and Shipping: Ship sample at room temperature for receipt at CEN4GEN within 24 hours of collection. Do not refrigerate or freeze.

Type: Dried Blood Spot
Specimen Requirements:
Minimum of three standard blood spot circles
Specimen Collection and Shipping: Ship sample at room temperature for receipt at CEN4GEN within 24 hours of collection. Do not refrigerate or freeze.

Type: Saliva

Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

SPECIAL INSTRUCTIONS

Parental samples may be requested to interpret the clinical significance of some findings.