Genetic testing

Banding and pairing alike chromosomes. Done in lithium heparin sample (14 days turnaround time)

Can show: aneuploidies, balanced/unbalanced translocations, large deletions/duplications

Good for:

• Down's (trisomy 21/unbalanced Robertsonian translocation in 2%): 47 **/XY +21
• Edward's (trisomy 18): 47 **/XY +18
• Patau's (trisomy 13): 47 **/XY +13
• Klinefelter's: 47 **Y
• Turner's: 45 X

Fluorescent in situ hybridisation

Attaches fluorescent tracers to specific DNA sequences

Can detect: aneuploidies, specific deletions and duplications, specific mutations

Chromosomal microarray. 

Can detect abnormal numbers of genes (should have 2)

Useful for: aneuploidies, unbalanced translocations, deletions/duplications

Quantitative fluorescent PCR

Rapid screen for common trisomies and sex chromosomes in neonates.

Done in 1-2mL EDTA sample with 48hr turnaround time. If abnormal, should be followed up with karyotyping.

Should have 2 peaks (for 2 different alleles) - in trisomies, have 3 peaks or increased size of 1 peak.

If pt likely to have a single gene defect but normal CMA and no abnormality seen on sequencing likely genes, can do whole exome sequencing.

Includes all exons, ultraconserved regions, regulatory regions, ncRNAs, enhancers, splice donor + acceptor regions.

Will show ALL abnormalities, including normal variants (normally 30,000 per exome):

• filter out common variants and variants unlikely to have an effect
• select only the variants in relevant disease genes
• look at parental genotypes/phenotypes and select variants with relevant inheritance (e.g. de novo, recessive)
• try and work out which gene is the cause- clinical input required