X-linked recessive inheritance

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X-linked recessive inheritance

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y chromosome) and in females who are homozygous for the gene mutation, see zygosity. Females with one copy of the mutated gene are carriers.

X-linked inheritance means that the gene causing the trait or the disorder is located on the X chromosome. Females have two X chromosomes while males have one X and one Y chromosome. Carrier females who have only one copy of the mutation do not usually express the phenotype, although differences in X-chromosome inactivation (known as skewed X-inactivation) can lead to varying degrees of clinical expression in carrier females, since some cells will express one X allele and some will express the other. The current estimate of sequenced X-linked genes is 499, and the total, including vaguely defined traits, is 983.[1]

Sex differences in phenotype/genotypes and frequency[edit]

In humans, generally men are affected and women are carriers for two reasons. The first is the simple statistical fact that if the X-chromosomes in a population carry a particular X-linked mutation at a frequency of 'f' (for example, 1%), then that will be the frequency that men are likely to express the mutation (since they have only one X), while women will express it at a frequency of f2 (for example 1% * 1% = 0.01%) since they have two X's and hence two chances to get the normal allele. Thus, X-linked mutations tend to be rare in women.[citation needed]

The second reason for female rarity is that women who express the mutation must have two X chromosomes that carry the trait, and they necessarily got one from their father, who would have also expressed the trait because he only had one X chromosome in the first place. If the trait lowers the probability of fathering a child or causes the father to choose to only have children with women who aren't carriers (so as to create daughters who are carriers rather than expressers, and then only if no genetic screening is used), then women become even less likely to express the trait.[citation needed]

A few scholars have suggested discontinuing the use of the terms dominant and recessive when referring to X-linked inheritance, stating that the highly variable penetrance of X-linked traits in females as a result of mechanisms such as skewed X-inactivation or somatic mosaicism is difficult to reconcile with standard definitions of dominance and recessiveness.[2]


Most common[edit]

The most common X-linked recessive disorders are:[3]

  • Red–green color blindness, a very common trait in humans and frequently used to explain X-linked disorders.[4] Between seven and ten percent of men and 0.49% to 1% of women are affected. Its commonness may be explained by its relatively benign nature. It is also known as daltonism.
  • Hemophilia A, a blood clotting disorder caused by a mutation of the Factor VIII gene and leading to a deficiency of Factor VIII. It was once thought to be the "royal disease" found in the descendants of Queen Victoria. This is now known to have been Hemophilia B (see below).[5][6]
  • Hemophilia B, also known as Christmas disease,[7] a blood clotting disorder caused by a mutation of the Factor IX gene and leading to a deficiency of Factor IX. It is rarer than hemophilia A. As noted above, it was common among the descendants of Queen Victoria.
  • Duchenne muscular dystrophy, which is associated with mutations in the dystrophin gene. It is characterized by rapid progression of muscle degeneration, eventually leading to loss of skeletal muscle control, respiratory failure, and death.
  • Becker's muscular dystrophy, a milder form of Duchenne, which causes slowly progressive muscle weakness of the legs and pelvis.
  • X-linked ichthyosis, a form of ichthyosis caused by a hereditary deficiency of the steroid sulfatase (STS) enzyme. It is fairly rare, affecting one in 2,000 to one in 6,000 males.[8]
  • X-linked agammaglobulinemia (XLA), which affects the body's ability to fight infection. XLA patients do not generate mature B cells.[9] B cells are part of the immune system and normally manufacture antibodies (also called immunoglobulins) which defends the body from infections (the humoral response). Patients with untreated XLA are prone to develop serious and even fatal infections.[10]
  • Glucose-6-phosphate dehydrogenase deficiency, which causes nonimmune hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications, chemicals, or foods. Commonly known as "favism", as it can be triggered by chemicals existing naturally in broad (or fava) beans.[11]

Less common disorders[edit]

Theoretically, a mutation in any of the genes on chromosome X may cause disease, but below are some notable ones, with short description of symptoms:

See also[edit]


  1. ^ "OMIM X-linked Genes". nih.gov. Archived from the original on 7 March 2016. Retrieved 3 May 2018.
  2. ^ Dobyns, William B.; Filauro, Allison; Tomson, Brett N.; Chan, April S.; Ho, Allen W.; Ting, Nicholas T.; Oosterwijk, Jan C.; Ober, Carole (2004). "Inheritance of most X-linked traits is not dominant or recessive, just X-linked". American Journal of Medical Genetics. 129A (2): 136. doi:10.1002/ajmg.a.30123. PMID 15316978.
  3. ^ GP Notebook - X-linked recessive disorders Archived 2011-06-13 at the Wayback Machine Retrieved on 5 Mars, 2009
  4. ^ "OMIM Color Blindness, Deutan Series; CBD". nih.gov. Archived from the original on 29 September 2009. Retrieved 3 May 2018.
  5. ^ Michael Price (8 October 2009). "Case Closed: Famous Royals Suffered From Hemophilia". ScienceNOW Daily News. AAAS. Archived from the original on 20 October 2013. Retrieved 9 October 2009.
  6. ^ Rogaev, Evgeny I.; Grigorenko, Anastasia P.; Faskhutdinova, Gulnaz; Kittler, Ellen L. W.; Moliaka, Yuri K. (2009). "Genotype Analysis Identifies the Cause of the 'Royal Disease'". Science. 326 (5954): 817. Bibcode:2009Sci...326..817R. doi:10.1126/science.1180660. PMID 19815722.
  7. ^ "Hemophilia B". Archived 2007-12-01 at the Wayback Machine National Hemophilia Foundation.
  8. ^ Carlo Gelmetti; Caputo, Ruggero (2002). Pediatric Dermatology and Dermatopathology: A Concise Atlas. T&F STM. p. 160. ISBN 1-84184-120-X.
  9. ^ "X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional". Archived from the original on 2008-02-18. Retrieved 2008-03-01.
  10. ^ "Diseases Treated at St. Jude". stjude.org. Archived from the original on 15 August 2007. Retrieved 3 May 2018.
  11. ^ "Favism - Doctor". patient.info. Archived from the original on 21 November 2017. Retrieved 3 May 2018.

External links[edit]

[Female X-linked disorders]