Traditionally, diagnosis of genetic causes of mental retardation (also referred to as developmental delay) has depended upon cytogenetic and/or FISH analysis of deletion syndromes. Recent technological advances have demonstrated the existence of many additional genetic variations/micro-deletion syndromes that cannot be detected by cytogenetics. A microarray-based system known as comparative genomic hybridization (CGH) provides a more comprehensive analysis of the genome in a single assay.
CGH can detect all of the ‘classic’ deletion syndromes and other genomic variations, deletions or duplications, including those that uniquely occur in a particular patient. The overall positive rate of detection is approximately three-fold higher than classic cytogenetic analysis.
CGC Genetics now offers CGH clinical testing services using an Agilent Technologies microarray/chip containing a customized 105,000-oligonucleotide probe set developed by its academic affiliate, the UMDNJ-New Jersey Medical School Institute of Genomic Medicine. The probes are specifically designed to detect genomic regions of interest related to mental retardation/developmental delay and other micro-deletion syndromes.
Testing requires as little as a 1 ml blood sample. Since quantitative copy number variants (CNVs) are common in normal individuals, testing of parents is highly recommended to ensure that a positive result is unique to the patient. Therefore, we recommend that samples be sent from patient and both parents whenever possible. Conformational testing of parents is included in the cost, as long as the parent samples are sent with the patient sample.
Additional Information:
Array-CGH can detect small DNA deletions or duplications invisible to standard chromosome analysis as well as nearly all disorders identified by karyotyping or multiple FISH tests including all known microdeletion/ duplication syndromes.
Custom Agilent 105K MR/DD array (1) – a 105,000 oligonucleotide array with very high density (average 5kb) in all subtelomeric and known microdeletion/duplication regions (2) while maintaining sufficient density in other regions of the genome (average 75kb) to provide comprehensive coverage for detection of mental retardation and developmental delay (MR/DD).
Balanced chromosome rearrangements (reciprocal translocations, Robertsonian translocations, inversions), point mutations, imbalances of regions not represented on this microarray and low grade mosaicism cannot be detected. All results should be interpreted within the context of a full cytogenetics analysis. Chromosomal changes smaller than 250kb are not reported because phenotypic consequences cannot be interpreted.
Indications for testing:
Array-CGH is indicated for patients with normal karyotypes and:
1-Unexplained mental retardation or developmental delay
2-Congenital abnormalities or dysmorphic features
3-Autism spectrum disorders, seizures or clinical features suggestive of a chromosomal anomaly
Array-CGH is indicated for patients with an abnormal karyotype and:
1-An unbalanced rearrangement, to precisely identify the endpoints of the duplication or deletion and the included genes
2-An apparently balanced rearrangement, to test for cryptic duplication or deletion at the rearrangement’s breakpoints
References:
1.American Journal of Medical Genetics 143: 824-829 (2007) an oligonucleotide based array-CGH system for detection of genome-wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation and developmental delay
2. Microdeletions/duplications
• 1p36
• Adrenal Hypoplasia Congenita
• Alagille Syndrome
• Angelman Syndrome
• Azospermia Factor A
• Azospermia Factor B
• Azospermia Factor C
• Bruton Agammaglobulinemia Tyrosine Kinase
• Beckwith-Wiedemann Syndrome
• Charcot-Marie Tooth 1A
• Cri-du-Chat Syndrome
• DiGeorge 1/VCF Syndrome
• DiGeorge 2 = 10p13
• Duchenne Muscular Dystrophy
• Glycerol Kinase Deficiency
• Greig syndrome [GLI3]
• Hereditary Neuropathy with Liability to Pressure Palsies
• Hypoparathyroidism,Sensorineural Deafness & Renal Dysplasia
• Kallman Syndrome
• Langer-Giedion Syndrome [EXT1 and TRPSI]
• Miller-Dieker Syndrome
• Potocki-Shaffer Syndrome [including Multiple Exostoses2]
• Neurofibromatosis 1
• Pelizaeus-Merzbacher Disease
• Polycystic Kidney Disease Type I
• Prader-Willi Syndrome
• Retinoblastoma 1
• Rubinstein-Taybi Syndrome
• Saethre-Chotzen Syndrome
• Sex determining region Y
• Smith-Magenis Syndrome
• Sotos Syndrome
• Steroid Sulfatase Deficiency
• Trichorhinophalangeal Syndrome
• Trisomy 13, 18, 21
• Tuberous Sclerosis 1
• Williams-Beuren Syndrome
• Wilm''s Tumor
• Wilms Tumor-Aniridia-Genitourinary anomalies-Mental retardation
• Wolf-Hirschorn syndrome
• Subtelomeric Regions
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