What is X-linked dominant inheritance?

The X-linked dominant inheritance is a pattern of genetic inheritance that occurs when there is a dominant gene on the differential segment of the X chromosome and therefore does not appear on the Y chromosome.

Also called X-linked dominance or inheritance linked to X chromosome dominant. It is less common than X-linked recessive inheritance, and both are more common than Y-linked inheritance.

In medicine, X-linked dominant inheritance indicates that a genetic disease is transmitted to offspring through a gene located on the X chromosome and that only one allele presenting the mutation is necessary for the disease to manifest, on the contrary. than recessive inheritance in which both alleles must present the mutation for the disease to manifest.

It is now known that the expression of genetic traits associated with the X chromosome can vary between different individuals due to mechanisms such as cell autonomous expression, biased inactivation of the X chromosome, clonal expansion or somatic mosaicism. Because of this, within the scientific community it has been suggested abandonment of the terms “dominant” and “recessive” when speaking of X-linked inheritance3.

inheritance pattern

The sex chromosomes are the X chromosome and the Y chromosome. The male sex has the XY pair of chromosomes and the female sex the XX pair. X-linked dominant inheritance is therefore determined by the sex of the parent carrying the gene. Considering that male offspring always inherit one X chromosome from their mother and one Y chromosome from their father and female offspring always inherit one X chromosome from their mother and one X chromosome from their father, X-linked dominant inheritance has the following characteristics:

  • Males pass it on to all of their female offspring and none of their male offspring.
  • Women pass it on to half of their female offspring and half of their male offspring.
  • All those affected have at least one affected parent (dominant inheritance).
  • Being a dominant gene, can appear in all generations

We can find the following situations:

Only the mother is a carrier

If the father is not affected and only the mother is the carrier of the gene in one of the alleles, she herself will have the disease and 50% of the offspring, either male or female, will inherit the gene and develop the disease. Sons and daughters have the same chance of inheriting the gene. The other 50% of the offspring will not inherit the gene and in this case there is also no difference between male and female offspring.

Only the father is a carrier

When the father is the carrier of the X-linked gene and the mother is not, it is the father who manifests the disease. In this case, the female offspring will always receive an affected X chromosome from the father and, therefore, 100% of daughters will be affected. On the contrary, none of the sons it will be affected by receiving the Y chromosome from the father and the X chromosome from the unaffected mother.

Both parents are carriers

If the father and the mother carry the X chromosome with the affected gene, both manifest the disease. In this case, the inheritance pattern determines a probability that 100% of daughters and 50% of sons inherit the disease. If the mother has the affected gene on both X chromosomes (homozygous), 100% of the sons and daughters will inherit the disease since they would always receive a copy of an affected X chromosome.

Associated diseases

Among the diseases associated with a dominant gene on the X chromosome we can find:

  • Vitamin D-resistant hypophosphatemia (also known as vitamin D-resistant rickets)
  • Rett syndrome
  • Alport syndrome (also known as hereditary nephritis. Only cases due to the COL4A5 gene is linked to the X chromosome)
  • Bloch-Sulzberger syndrome (also known as pigment incontinence)
  • Giuffrè-Tsukahara syndrome4
  • Focal dermal hypoplasia (also known as Goltz syndrome)
  • Androgen insensitivity syndrome (also known as testicular feminization)
  • Aicardi syndrome
  • X-linked dominant erythropoietic protoporphyria
  • X fragile syndrome
  • CHILD syndrome (Congenital hemidysplasia with ichthyosiform erythroderma and limb defects)
  • Lujan–Fryns syndrome (Marfanoid habitus with X-linked intellectual deficiency)
  • Orofaciodigital syndrome type 1
  • Craniofrontonasal dysplasia

Other disorders, such as synesthesiaare also thought to be X-linked dominant traits, although this remains to be determined exactly.

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