The most frequent combinations of the X-linked recessive mode of inheritance are as follows:
1. The mother is homozygous and normal (XX); the father is hemizygous and affected (X’Y). (Here X’ indicates the chromosome carrying the defective gene and X indicates the normal chromosome). All of the sons of this union will be normal and they will inherit the normal gene by way of the maternal X-chromosome.
All daughters, however, are heterozygous (X’X); the defective gene is located on the paternal X’ chromosome. Half the sons of these daughters will inherit the defective gene.
2. The mother is a heterozygous carrier (X’X), herself phenotypically normal. The father is normal (XY). In this case, half of the sons will be affected (X’Y), whereas all the daughters will be normal. However, half of the daughters will be heterozygous (X’X) carriers or conductors.
3. If an affected homozygous woman marries a normal man, all the sons will be affected, whereas all the daughters will be phenotypically normal conductors or carriers.
Therefore, the X-chromosomal recessive mode of inheritance is characterised by the fact that, especially with rare diseases, almost only men are affected. The path of inheritance, however, runs only via the normal daughters of sick fathers and the half-normal sisters of sick men.
This situation changes only if the brothers’ anomaly can be traced to a new mutation, in which case the sisters will not be the conductors. The worst situation is that all the daughters of affected fathers will be the conductors.
The second sex-linked mode of inheritance is the X-chromosomal dominant one. The mode differs from the X-chromosomal recessive mode in that not only the hemizygotes (male) but also the heterozygotes (females) manifest the anomaly. Both men and women are affected evenly when the anomaly is a rare one.
All the sons of affected fathers are uneffected but all the daughters are trait- bearers as well as half of the sisters of the father. Among the children of the female patients there is a 1: 1 segregation as in case of autosomal dominant mode of inheritance i.e. independent of sex.
So, in brief, male patients must have inherited the trait from the mother, among their siblings there is a 1: 1 segregation independent of sex. Female patients may have inherited the defective gene from either father or mother.
So, the above facts alone serve to demonstrate that the insufficient data may make it highly difficult to differentiate between the X- chromosomal dominant and the autosomal dominant modes of inheritance.