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.[citation needed]

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]

Patterns of inheritance

Patterns of X-linked recessive inheritance in a royal family

In humans, inheritance of X-linked recessive traits follows a unique pattern made up of three points.

  • The first is that affected fathers cannot pass X-linked recessive traits to their sons because fathers give Y chromosomes to their sons. This means that males affected by an X-linked recessive disorder inherited the responsible X chromosome from their mothers.
  • Second, X-linked recessive traits are more commonly expressed in males than females.[2] This is due to the fact that males possess only a single X chromosome, and therefore require only one mutated X in order to be affected. Women possess two X chromosomes, and thus must receive two of the mutated recessive X chromosomes (one from each parent). A popular example showing this pattern of inheritance is that of the descendants of Queen Victoria and the blood disease hemophilia.[3]
  • The last pattern seen is that X-linked recessive traits tend to skip generations, meaning that an affected grandfather will not have an affected son, but could have an affected grandson through his daughter.[4] Explained further, all daughters of an affected man will obtain his mutated X, and will then be either carriers or affected themselves depending on the mother. The resulting sons will either have a 50% chance of being affected (mother is carrier), or 100% chance (mother is affected). It is because of these percentages that we see males more commonly affected than females.

Recessive/dominant terminology

A few scholars have suggested discontinuing the use of the terms dominant and recessive when referring to X-linked inheritance.[5] The possession of two X chromosomes in females leads to dosage issues which are alleviated by X-inactivation.[6] 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, scholars have suggested referring to traits on the X chromosome simply as X-linked.[5]


Most common

a)Male with hemophilia B with an open wound b)postoperative day 4 view, hemostasis and hematoma removal were performed twice, on the fifth and seventh postoperative days c) postoperative 1 year 8 month view

The most common X-linked recessive disorders are:[7]

  • Red–green color blindness, a very common trait in humans and frequently used to explain X-linked disorders.[8] 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).[9][10]
  • Hemophilia B, also known as Christmas disease,[11] 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.[12]
  • X-linked agammaglobulinemia (XLA), which affects the body's ability to fight infection. XLA patients do not generate mature B cells.[13] 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.[14]
  • 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.[15]

Less common disorders

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


  1. "OMIM X-linked Genes". nih.gov. Archived from the original on 7 March 2016. Retrieved 3 May 2018.
  2. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. National Center for Biotechnology Information. 8 July 2009. Archived from the original on 27 November 2022. Retrieved 9 June 2020.
  3. "History of Bleeding Disorders". National Hemophilia Foundation. 2014-03-04. Archived from the original on 2020-11-12. Retrieved 2020-06-09.
  4. Pierce, Benjamin A. (2020). Genetics: A Conceptual Approach. Macmillan Learning. pp. 154–155. ISBN 978-1-319-29714-5.
  5. 5.0 5.1 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): 136–43. doi:10.1002/ajmg.a.30123. PMID 15316978. S2CID 42108591.
  6. Shvetsova, Ekaterina; Sofronova, Alina; Monajemi, Ramin; Gagalova, Kristina; Draisma, Harmen H. M.; White, Stefan J.; Santen, Gijs W. E.; Chuva de Sousa Lopes, Susana M.; Heijmans, Bastiaan T.; van Meurs, Joyce; Jansen, Rick (March 2019). "Skewed X-inactivation is common in the general female population". European Journal of Human Genetics. 27 (3): 455–465. doi:10.1038/s41431-018-0291-3. ISSN 1476-5438. PMC 6460563. PMID 30552425.
  7. GP Notebook - X-linked recessive disorders Archived 2011-06-13 at the Wayback Machine Retrieved on 5 Mars, 2009
  8. "OMIM Color Blindness, Deutan Series; CBD". nih.gov. Archived from the original on 29 September 2009. Retrieved 3 May 2018.
  9. 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.
  10. 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. S2CID 206522975.
  11. "Hemophilia B". Archived 2007-12-01 at the Wayback Machine National Hemophilia Foundation.
  12. Carlo Gelmetti; Caputo, Ruggero (2002). Pediatric Dermatology and Dermatopathology: A Concise Atlas. T&F STM. p. 160. ISBN 1-84184-120-X.
  13. "X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional". Archived from the original on 2008-02-18. Retrieved 2008-03-01.
  14. "Diseases Treated at St. Jude". stjude.org. Archived from the original on 15 August 2007. Retrieved 3 May 2018.
  15. "Favism - Doctor". patient.info. Archived from the original on 21 November 2017. Retrieved 3 May 2018.

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