Color Blindness Inheritance: Why Three Affected Brothers & One Unaffected Is Not So Unusual

Congenital red-green color blindness is typically X-linked recessive (OPN1LW/OPN1MW genes on Xq28).

• Males (XY): One mutant allele → affected.
• Females (XX): Need two mutant alleles → affected; one → carrier (usually asymptomatic due to X-inactivation mosaicism).

Expected Patterns from a Carrier Mother

• Each son: 50% chance affected.
• Probability of 3/4 sons affected = C(4,3) × 0.5⁴ = 25%.
• Probability of 4/4 affected = 6.25%.

So 3 affected + 1 unaffected is possible by chance (25%)—not statistically "unlikely," just notable. If the father is affected, all daughters are carriers; no sons are affected (father gives Y to sons).

Alternative Explanations

• De novo mutation in one brother.
• Different mutation types (e.g., one has blue-cone monochromacy).
• Non-genetic cause (optic neuropathy, toxicity) in affected brothers.
• Incomplete penetrance/expressivity (rare for opsin mutations).

Genetic testing (panel for OPN1LW, OPN1MW, OPN1SW) clarifies the diagnosis.