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autosomal recessive diseases

Thursday 2 March 2006

Definition: Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder.

Autosomal recessive inheritance is the single largest category of mendelian disorders. Because autosomal recessive disorders result only when both alleles at a given gene locus are mutants, such disorders are characterized by the following features:

- (1) The trait does not usually affect the parents, but siblings may show the disease;
- (2) siblings have one chance in four of being affected (i.e., the recurrence risk is 25% for each birth);
- (3) if the mutant gene occurs with a low frequency in the population, there is a strong likelihood that the proband is the product of a consanguineous marriage.

In contrast to those of autosomal dominant diseases, the following features generally apply to most autosomal recessive disorders.

- The expression of the defect tends to be more uniform than in autosomal dominant disorders.
- Complete penetrance is common.
- Onset is frequently early in life.
- Although new mutations for recessive disorders do occur, they are rarely detected clinically. Since the individual with a new mutation is an asymptomatic heterozygote, several generations may pass before the descendants of such a person mate with other heterozygotes and produce affected offspring.
- In many cases, enzyme proteins are affected by a loss of function. In heterozygotes, equal amounts of normal and defective enzyme are synthesized. Usually the natural "margin of safety" ensures that cells with half their usual complement of the enzyme function normally.

Autosomal recessive disorders include almost all inborn errors of metabolism (genetic metabolic diseases).

Some examples

- cystic fibrosis
- sickle cell anemia
- Tay-Sachs disease
- spinal muscular atrophy (SMAs)