Lesch–Nyhan syndrome (OMIM 300322) is a rare X-linked recessive disorder that produces severe mental retardation, spastic cerebral palsy, and self-mutilation.


What is the probability that the first son of a woman whose brother has Lesch–Nyhan syndrome will be affected?

Verified step by step guidance

1. Understand the inheritance pattern: Lesch–Nyhan syndrome is an X-linked recessive disorder. This means the gene responsible for the condition is located on the X chromosome, and males (XY) are more likely to be affected because they have only one X chromosome.
2. Determine the genetic status of the woman: Since her brother has Lesch–Nyhan syndrome, her mother must be a carrier (heterozygous for the mutation). The woman has a 50% chance of inheriting the affected X chromosome from her mother, making her a carrier.
3. Consider the genetic contribution to the son: If the woman is a carrier, there is a 50% chance she will pass on the affected X chromosome to her child. Sons inherit their X chromosome from their mother and their Y chromosome from their father.
4. Combine probabilities: The probability that the woman is a carrier (50%) and the probability that she passes on the affected X chromosome to her son (50%) must be multiplied to determine the overall probability that her son will be affected.
5. Express the final probability: Multiply the probabilities from the previous step (0.5 × 0.5) to calculate the likelihood that her first son will inherit Lesch–Nyhan syndrome. This step provides the final probability but does not calculate the numerical result explicitly.

Key Concepts

X-linked Recessive Inheritance

Lesch–Nyhan syndrome is an X-linked recessive disorder, meaning the gene responsible for the condition is located on the X chromosome. Males, having one X and one Y chromosome, are more likely to express the disorder if they inherit the affected X. Females, with two X chromosomes, can be carriers if they have one affected X but typically do not show symptoms unless both X chromosomes are affected.

Carrier Status

In the context of X-linked disorders, a carrier female has one normal X chromosome and one affected X chromosome. If her brother has Lesch–Nyhan syndrome, it indicates that he inherited the affected X from their mother, making her a carrier. The probability of her passing the affected X to her son is 50%, as sons inherit their X chromosome from their mother.

Punnett Square

A Punnett square is a tool used in genetics to predict the probability of offspring inheriting particular traits from their parents. In this case, it can be used to visualize the potential genetic combinations between a carrier mother (X^H X) and a normal father (X Y). This helps in determining the likelihood of their son inheriting the affected X chromosome and thus being affected by Lesch–Nyhan syndrome.