X-linked dominant inheritance

X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type. In medicine, X-linked dominant inheritance indicates that a gene responsible for a genetic disorder is located on the X chromosome, and only one copy of the allele is sufficient to cause the disorder when inherited from a parent who has the disorder. In this case, someone who expresses an X-linked dominant allele will exhibit the disorder and be considered affected.

X-linked dominant traits do not necessarily affect males more than females (unlike X-linked recessive traits). The exact pattern of inheritance varies, depending on whether the father or the mother has the trait of interest. All fathers that are affected by an X-linked dominant disorder, will have affected daughters, but not affected sons. However, if the mother is also affected then sons will have a chance of being affected, depending on whether a dominant or recessive X chromosome is passed on. When the son is affected the mother will always be affected.

Some scholars have suggested discontinuing the terms dominant and recessive when referring to X-linked inheritance due to the multiple mechanisms that can result in the expression of X-linked traits in females, which include cell autonomous expression, skewed X-inactivation, clonal expansion, and somatic mosaicism.

Genetics

As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the sex of the parent carrying a specific gene and can often seem complex. This is due to the fact that, typically, females have two copies of the X-chromosome, while males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.

Males can only get an X chromosome from their mother whilst females get an X chromosome from both parents. As a result, females tend to show higher prevalence of X-linked dominant disorders because they have more of a chance to inherit a faulty X chromosome.

Inheritance

X-linked dominant inheritance works differently depending upon whether the mother (left image) or father (right image) is the carrier of a gene that causes a disease or disorder.

In X-linked dominant inheritance, when the mother alone is the carrier of a mutated, or defective gene associated with a disease or disorder; she herself will have the disorder. Her children will inherit the disorder as follows:

• Of her daughters and sons: 50% will have the disorder, 50% will be completely unaffected. Children of either sex have an even chance of receiving either of their mother's two X chromosomes, one of which contains the defective gene in question.

When the father alone is the carrier of a defective gene associated with a disease or disorder, he too will have the disorder. His children will inherit the disorder as follows:

• Of his daughters: 100% will have the disorder, since all of his daughters will receive one copy of his single X chromosome.
• Of his sons: none will have the disorder; sons do not receive an X chromosome from their father.

If both parents were carriers of a defective gene associated with a disease or disorder, they would both have the disorder. Their children would inherit the disorder as follows:

• Of their daughters: 100% will have the disorder, since all of the daughters will receive a copy of their father's X chromosome.
• Of the sons: 50% will have the disorder, 50% will be completely unaffected. Sons have an equal chance of receiving either of their mother's X chromosomes.

In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents. Were this to occur with an X-linked dominant disorder, that daughter would likely experience a more severe form.

Some X-linked dominant conditions such as Aicardi Syndrome are fatal to boys, therefore only girls with these conditions survive, or boys with Klinefelter's syndrome (and hence have more than one X chromosome).

List of dominant X-linked diseases

• Vitamin D resistant rickets: X-linked hypophosphatemia
• Rett syndrome (95% of cases are due to sporadic mutations)
• Most cases of Alport syndrome
• Incontinentia pigmenti
• Giuffrè–Tsukahara syndrome
• Goltz syndrome
• X-linked dominant protoporphyria
• Fragile X syndrome

See also

• X-linked hypophosphatemia
• Rett syndrome
• Sex linkage
• Incontinentia pigmenti [1]
• X-linked recessive inheritance