X連鎖隱性遺傳

X連鎖隱性遺傳（X-linked recessive inheritance）是孟德爾遺傳一種模式，其中X染色體基因突變導致表型總是在男性中表達（對於基因突變來說必然是純合，因為有一條X和一條Y染色體），在基因突變純合的女性中，參見合子。攜帶一份突變基因的女性是攜帶者。

X連鎖隱性遺傳

Patterns of X-linked recessive inheritance in a royal family

X連鎖遺傳是指導致性狀或疾病的基因位於X染色體上。女性有兩X染色體，而男性有一X染色體和一Y染色體。只有一個突變拷貝的攜帶者女性通常不會表現出表型，儘管X染色體失活（英语：X-chromosome inactivation）（傾斜X失活（英语：skewed X-inactivation））的差異會導致攜帶者不同程度的臨床表現女性，因為有些細胞會表達一個 X等位基因，而有些細胞會表達另一個。目前對已測序的X連鎖基因的估計是499個，包括模糊定義的性狀在內的總數是983個。^[1]

繼承模式

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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.

Pushback on 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]

Examples

Most common

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

参见：X-linked intellectual disability

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:

• Adrenoleukodystrophy; leads to progressive brain damage, failure of the adrenal glands and eventually death.
• Alport syndrome; glomerulonephritis, endstage kidney disease, and hearing loss. A minority of Alport syndrome cases are due to an autosomal recessive mutation in the gene coding for type IV collagen.
• Androgen insensitivity syndrome; variable degrees of undervirilization and/or infertility in XY persons of either sex
• Barth syndrome; metabolism distortion, delayed motor skills, stamina deficiency, hypotonia, chronic fatigue, delayed growth, cardiomyopathy, and compromised immune system.
• Blue cone monochromacy; low vision acuity, color blindness, photophobia, infantile nystagmus.
• Centronuclear myopathy; where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.
• Charcot–Marie–Tooth disease (CMTX2-3); disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease.
• Coffin–Lowry syndrome; severe intellectual disability sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis as well as auditory and visual abnormalities.
• Fabry disease; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement.
• Hunter syndrome; potentially causing hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen.
• Hypohidrotic ectodermal dysplasia, presenting with hypohidrosis, hypotrichosis, hypodontia
• Kabuki syndrome (the KDM6A variant); multiple congenital anomalies and intellectual disability.
• Spinal and bulbar muscular atrophy; muscle cramps and progressive weakness
• Lesch–Nyhan syndrome; neurologic dysfunction, cognitive and behavioral disturbances including self-mutilation, and uric acid overproduction (hyperuricemia)
• Lowe syndrome; hydrophthalmia, cataracts, intellectual disabilities, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets
• Menkes disease; sparse and coarse hair, growth failure, and deterioration of the nervous system
• Nasodigitoacoustic syndrome; misshaped nose, brachydactyly of the distal phalanges, sensorineural deafness
• Nonsyndromic deafness; hearing loss
• Norrie disease; cataracts, leukocoria along with other developmental issues in the eye
• Occipital horn syndrome; deformations in the skeleton
• Ocular albinism; lack of pigmentation in the eye
• Ornithine transcarbamylase deficiency; developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen
• Oto-palato-digital syndrome; facial deformities, cleft palate, hearing loss
• Siderius X-linked mental retardation syndrome; cleft lip and palate with intellectual disability and facial dysmorphism, caused by mutations in the histone demethylase PHF8
• Simpson–Golabi–Behmel syndrome; coarse faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip
• Spinal muscular atrophy caused by UBE1 gene mutation; weakness due to loss of the motor neurons of the spinal cord and brainstem
• Wiskott–Aldrich syndrome; eczema, thrombocytopenia, immune deficiency, and bloody diarrhea
• X-linked severe combined immunodeficiency (SCID); infections, usually causing death in the first years of life
• X-linked sideroblastic anemia; skin paleness, fatigue, dizziness and enlarged spleen and liver.

另見

• 伴性遺傳
• X連鎖顯性遺傳

參考

1. OMIM X-linked Genes. nih.gov. [3 May 2018]. （原始内容于7 March 2016）. 
2. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. National Center for Biotechnology Information. 8 July 2009 [9 June 2020]. （原始内容于2022-11-27）. 
3. History of Bleeding Disorders. National Hemophilia Foundation. 2014-03-04 [2020-06-09]. （原始内容于2020-11-12） （英语）. 
4. Pierce, Benjamin A. Genetics: A Conceptual Approach. Macmillan Learning. 2020: 154–155. ISBN 978-1-319-29714-5. 
5. Dobyns, William B.; Filauro, Allison; Tomson, Brett N.; Chan, April S.; Ho, Allen W.; Ting, Nicholas T.; Oosterwijk, Jan C.; Ober, Carole. Inheritance of most X-linked traits is not dominant or recessive, just X-linked. American Journal of Medical Genetics. 2004, 129A (2): 136–43. PMID 15316978. S2CID 42108591. doi:10.1002/ajmg.a.30123. 
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. Skewed X-inactivation is common in the general female population. European Journal of Human Genetics. March 2019, 27 (3): 455–465. ISSN 1476-5438. PMC 6460563  . PMID 30552425. doi:10.1038/s41431-018-0291-3   （英语）. 
7. GP Notebook - X-linked recessive disorders 互联网档案馆的，存档日期2011-06-13. Retrieved on 5 Mars, 2009
8. OMIM Color Blindness, Deutan Series; CBD. nih.gov. [3 May 2018]. （原始内容于29 September 2009）. 
9. Michael Price. Case Closed: Famous Royals Suffered From Hemophilia. ScienceNOW Daily News. AAAS. 8 October 2009 [9 October 2009]. （原始内容于20 October 2013）. 
10. Rogaev, Evgeny I.; Grigorenko, Anastasia P.; Faskhutdinova, Gulnaz; Kittler, Ellen L. W.; Moliaka, Yuri K. Genotype Analysis Identifies the Cause of the 'Royal Disease'. Science. 2009, 326 (5954): 817. Bibcode:2009Sci...326..817R. PMID 19815722. S2CID 206522975. doi:10.1126/science.1180660. 
11. "Hemophilia B". 互联网档案馆的，存档日期2007-12-01. National Hemophilia Foundation.
12. Carlo Gelmetti; Caputo, Ruggero. Pediatric Dermatology and Dermatopathology: A Concise Atlas. T&F STM. 2002: 160. ISBN 1-84184-120-X. 
13. X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional. [2008-03-01]. （原始内容于2008-02-18）. 
14. Diseases Treated at St. Jude. stjude.org. [3 May 2018]. （原始内容于15 August 2007）. 
15. Favism - Doctor. patient.info. [3 May 2018]. （原始内容于21 November 2017）. 

外部鏈接

• from the Wellcome Trust

[Female X-linked disorders]

• Sex-linked recessive: MedlinePlus Medical Encyclopedia （页面存档备份，存于互联网档案馆）