X linked Recessive Inheritance

The ways by which a genetic trait or condition is caused via a mutated (i.e. changed) gene present on the X chromosome can be passed down (i.e. inherited) from parent to child. In X-linked recessive inheritance, a daughter can inherit a single mutated gene on the X chromosome from one of her parents. The X chromosome inherited by daughters comes from the other parent, this will cancel the effect of the mutation, and the daughter will most likely not have the genetic condition. The daughter will be affected by the condition, only when she inherits a mutated copy of the gene from both the parents. Fathers usually do not pass X-linked recessive conditions to their sons. In sons, the genetic condition is more likely to occur when he inherits a mutated gene on the X chromosome from his mother. X-linked recessive conditions are more commonly seen in males.

Patterns for X-linked Recessive Inheritance

After completing the filling of the genotypes for individuals in various family trees which exhibit this mode of inheritance, some patterns that  are mainly noticed are discussed below:

  • The trait is generally more common in males rather than in females.
  • If a mother possesses the trait, then all of her sons will also have it.
  • No male to the male transmission can be observed.
  • It possesses the same inheritance patterns as those of autosomal recessive human females.
  • The son of a female carrier has a 50%  probability of having the trait.
  • Mothers of males who are having the trait can be either heterozygous carriers or homozygous and express the trait.

X-linked Disorders in Females

In a few cases, females might get affected by X linked recessive disorders. This fact is explainable by one of the following possibilities discussed below:

  • Heterozygosity: X inactivation is a sudden phenomenon that involves a mutant allele having X and a normal allele X in equal ratios in the heterozygous female. It can be possible that the active X chromosome in the majority of the cells of a heterozygous female is the one that possesses a mutant allele (skewed X inactivation), this results in a disorder expression; this can be seen in the case of Duchenne muscular dystrophy and haemophilia A.
  • Homozygosity: When both the X chromosomes of females possess a mutant allele, as seen in haemophilia A and ichthyosis.
  • Translocations: A female might be affected if she is having a translocation involving an autosome and one of the X chromosomes and the translocation disturbs a gene on an X chromosome. This pattern has been observed in Duchenne muscular dystrophy. 
  • Females have only a single X chromosome (Turner syndrome), that bears a mutant allele. Hemophilia has been reported in the girl infant with the turner syndrome.

Common X-linked Disorders

Red-green colour blindness: is a very common trait that usually affects at least 10 percent of men and only one percent of women. The red-green colour blindness can be partial or complete, but complete colour blindness is much less common.

  • Hemophilia A: this disorder is a result of a mutation in the factor VIII gene. Hemophilia A might be inherited or might occur as a result of a spontaneous mutation. Acquired haemophilia A can be observed if a patient develops antibodies against factor VIII. The main cause of morbidity and mortality in haemophilia A is haemorrhage, which ranges from mild to severe. However rare, transfusions of blood might sometimes lead to transmission of HIV and hepatitis C; this was very common during the 1980s and 1990s.
  • Duchene muscular dystrophy: is related to a mutation in the dystrophin gene and is observed as profound muscle weakness, resulting in respiratory failure and death.
  • X-linked agammaglobulinemia: leads to an inability to make plasma cells and antibodies. Every individual develops susceptibility to a wide range of infections that can be fatal.
  • Alport syndrome: refers to an X-linked disorder that usually has a heterogeneous presentation. Its pathology includes the basement membrane, and mainly affects the basement membranes of the kidney in addition to the eyes and cochlea. A form of mutation occurs in the type IV collagen gene.
  • Charcot-Marie-Tooth disease: this is the most common form of an inherited neurological disorder that is generalized by an inherited neuropathy in the absence of any metabolic or biochemical dysfunction. The disorder possesses different penetrance, and there are also reports of spontaneous mutations. The age of presentation does not vary, but the onset of the disorder is mainly within the first two decades of life.
  • Fabry disease: it is also an X-linked disorder that includes the lysosomes. This type of disorder results in an excessive accumulation of neutral glycosphingolipids in the vascular endothelium, smooth muscle, and epithelial cells. Further accumulation of glycosphingolipids leads to various dysfunction in almost every organ in the body. A young person who is having a history of skin lesions, renal failure, stroke, or a heart attack, must think about Fabry disease.
  • Other less common X-linked disorders involve adrenoleukodystrophy, Kabuki syndrome, and Lesch-Nyhan syndrome.

Conclusion

In X-linked recessive inheritance, the mutated gene is located on the X chromosome. Duchenne muscular dystrophy, some forms of colour-blindness and haemophilia A are some good examples of X-linked recessive disorders. A man suffering from X-linked recessive disorder will pass his unaffected Y chromosome to his sons, and none of the offspring will be affected. He will pass his affected X chromosome (along with the abnormal gene) to his daughters, and in this case, all will be the carriers of the disease. His daughters might possess no symptoms or only mild symptoms of the disorder, and they may further pass the abnormal gene to their children.

Related Posts