Patients with an autosomal recessive disorder (eg, cystic fibrosis) may be homozygotes or compound heterozygotes (that is, with different pathogenic mutations on each chromosome). The specific mutation detected may predict disease severity.
The size of deletions, duplications or variable repeat regions (eg, fragile X syndrome, myotonic dystrophy) may allow prediction of likely severity.
Predictions based on family studies using DNA polymorphisms have a variable degree of uncertainty due to the possibility of chromosomal crossing over between the gene and the polymorphic marker (eg, in many families with haemophilia A, the mutation cannot be identified directly and family studies using DNA polymorphisms are required).
A negative result on a fetus or a potential carrier does not necessarily exclude the possibility.
Mitochondrial abnormalities may not be present in all copies of the genome (heteroplasmy); liver and skeletal muscle are the most reliable tissues for the detection of mitochondrial genetic disorders.
A set of polymorphic markers may be used to validate the fetal origin of cells from chorionic villi or amniotic fluid. They are also used to document the unusual occurrence of uniparental disomy, that is both chromosomes derived from the same parent eg, Prader Willi and Angelman syndromes.