Two siblings with osteogenesis imperfect, but their parents are normal. Mechanism of inheritance is –
**Core Concept**
Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones, blue sclera, and other skeletal abnormalities. The disease is caused by mutations in the COL1A1 or COL1A2 genes, which encode for type I collagen. Inheritance patterns of OI can be complex, involving various genetic mechanisms.
**Why the Correct Answer is Right**
Germ line mosaicism occurs when a parent has a mixture of normal and abnormal cells in their reproductive cells (sperm or eggs). This means that some of the parent's offspring may inherit the mutated gene, while others may not. In this case, the siblings have OI, but their parents are normal, suggesting that the mutation is not inherited from them. Instead, the mutation is present in the parent's germ cells, allowing for the transmission of the disease to their offspring through a process called germ line mosaicism.
**Why Each Wrong Option is Incorrect**
**Option A:** Anticipation refers to the phenomenon where the symptoms of a genetic disorder become apparent at an earlier age in successive generations. While anticipation can occur in some genetic disorders, it is not the primary mechanism explaining the inheritance of OI in this scenario.
**Option B:** Genomic imprinting is a process where the expression of a gene is influenced by its parental origin. However, the COL1A1 and COL1A2 genes are not subject to genomic imprinting, making this option incorrect.
**Option D:** New mutation implies that the mutation occurred spontaneously in one of the siblings. However, the fact that both siblings have OI suggests that the mutation is present in the family and has been passed down from a parent, making a new mutation an unlikely explanation.
**Clinical Pearl / High-Yield Fact**
Germ line mosaicism can occur in any parent, regardless of their age or fertility status. This highlights the importance of considering complex inheritance patterns in genetic disorders, especially when parents appear to be unaffected.
**Correct Answer Line**
✓ Correct Answer: C. Germ line mosaicism