Review Question - QID 211043

This is a patient with meconium ileus with a genetic abnormality that is characteristic of the most common form of cystic fibrosis, the phenylalanine 508 deletion from chromosome 7. For cystic fibrosis patients with unaffected parents, a sibling would have a 50% chance of being a carrier for the disease.

Cystic fibrosis follows an autosomal recessive inheritance pattern. Autosomal recessive inheritance requires homozygosity of a minor allele at a single locus in order for phenotypic manifestation to occur. Mendelian genetics dictate that heterozygous carriers of a monogenic disease bear offspring in a ratio of 1:2:1 for wild-type:heterozygous:homozygous for the minor/mutated allele. Thus, 2 unaffected parents who are carriers of an autosomal recessive disease have a 50% chance of having a child who is also a carrier. It may also be possible that the offspring acquired de novo mutations that are not inherited from either parent. In the case of an acquired de novo mutation, the probability of giving birth to another child with the same autosomal recessive disease is highly unlikely.

Incorrect Answers:
Answer 1: Approximately 0% would be the probability if the disease resulted from a de novo mutation.

Answer 2: 25% would be the probability of the sibling being homozygous for the disease allele or homozygous for the wild-type allele.

Answer 4: 67% would be the probability if the mutation were homozygous lethal. This refers to the situation when homozygosity for the disease allele is incompatible with life; thus, a living child must either be homozygous for the wild-type allele or heterozygous.

Answer 5: 100% would be the probability if the twins were identical. However, these are dizygotic twins.

Bullet Summary:
Unaffected parents who are carriers of an autosomal recessive disease have a 50% chance of bearing a child who is also a carrier.