Sex-linked diseases

A monogenic disease has a sex-linked hereditary recessive transmission when the gene
involved is located on a sexual chromosome (X or Y); if the gene is located on the X chromosome, it is a X-linked transmission and the pathological condition occurs usually only in the male individuals because they have only the X chromosome with the mutated allele (hemizygous); examples of X-linked recessive diseases are the Duchenne muscular dystrophy, fragile-X syndrome, Hemophilia A and B.
Female individuals with the gene copies altered (heterozygous) usually don't manifest the disease and they are "healthy carrier”. In the fig.1 a female individual "healthy carrier" and a normal male; for a specific gene of X chromosome the normal allele is point out with X and the mutated allele with x. An heterozygous mother (Xx) with a mutation produces oocytes with a X normal allele or a x mutated allele. The father produces spermatozoa with X allele or with the Y chromosome. A "healthy carrier" (heterozygous) female and a normal male can generate:
- the 50% of affected male children (xY), and they can transmit the mutated allele x to all of possible daughters.
- the 50% of heterozygous mother’s daughters will be heterozygous and they have a probability of 50% to transmit the X chromosome with the mutated allele (x) to their children.

Trasmissione ereditaria di una malattia genetica legata al cromosoma X

Fig.1 - X-linked hereditary recessive transmission

The X-linked diseases rarely can hit also the women. A pathology can shows:
- in heterozygous mother’s daughters (homozygous xx) for the mutation (Xx) and affected father (xY), because they have a x mutated allele from both parents;
- in the heterozygous female (Xx) in which it is inactivated preferentially the X chromosome with the normal allele;
- in female with X chromosome monosomy (Turner syndrome) in which it is present only X chromosome with mutation.