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X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type. In medicine, X-linked dominant inheritance indicates that a gene responsible for a genetic disorder is located on the X chromosome, and only one copy of the allele is sufficient to cause the disorder when inherited from a parent who has the disorder.
X-linked dominant traits do not necessarily affect males more than females (unlike X-linked recessive traits). The exact pattern of inheritance varies, depending on whether the father or the mother has the trait of interest. All daughters of an affected father will also be affected but none of his sons will be affected (unless the mother is also affected). In addition, the mother of an affected son is also affected (but not necessarily the other way round).
As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the gender of the parent carrying a specific gene and can often seem complex. This is due to the fact that, typically, females have two copies of the X-chromosome, while males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.
|X-linked dominant inheritance works differently depending upon whether the mother (left image) or father (right image) is the carrier of a gene that causes a disease or disorder.|
In X-linked dominant inheritance, when the mother alone is the carrier of a mutated, or defective gene associated with a disease or disorder; she herself will have the disorder. Her children will inherit the disorder as follows:
- Of her daughters and sons: 50% will have the disorder, 50% will be completely unaffected. Children of both genders have an even chance of receiving either of their mother's two X chromosomes, one of which contains the defective gene in question.
When the father alone is the carrier of a defective gene associated with a disease or disorder, he too will have the disorder. His children will inherit the disorder as follows:
- Of his daughters: 100% will have the disorder, since all of his daughters will receive one copy of his single X chromosome.
- Of his sons: none will have the disorder; sons do not receive an X chromosome from their father.
If both parents were carriers of a defective gene associated with a disease or disorder, they would both have the disorder. Their children would inherit the disorder as follows:
- Of their daughters: 100% will have the disorder, since all of the daughters will receive a copy of their father's X chromosome.
- Of the sons: 50% will have the disorder, 50% will be completely unaffected. Sons have an equal chance of receiving either of their mother's X chromosomes.
In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents. Were this to occur with an X-linked dominant disorder, that daughter would likely experience a more severe form.
Some X-linked dominant conditions such as Aicardi Syndrome are fatal to boys, therefore only girls with these conditions survive. Similarly, individuals with Klinefelter's Syndrome are referred to as "47,XXY Males".
- Vitamin D resistant rickets: X-linked hypophosphatemia
- Rett syndrome
- Fragile X syndrome
- Most cases of Alport syndrome
- Incontinentia pigmenti
- Giuffrè–Tsukahara syndrome
- Charcot–Marie–Tooth disease
- ↑ PMID 2018074 (PMID 2018074)
- ↑ The more frequent presentation of Alport Syndrome appear from mutations in the COL4A5 gene, which are inherited in an X-linked dominant form; see Jais JP et al. X-Linked Alport Syndrome: Natural History and Genotype-Phenotype Correlations in Girls and Women Belonging to 195 Families: A “European Community Alport Syndrome Concerted Action” Study J Am Soc Nephrol. 2003 Oct;14(10):2603-10. Accessed 27 May 2012.
- ↑ Ashwin, B. Dalal, Anujit Sarkar, T. Padma Priya, Madhusudan R. Nandineni (2010). Giuffrè–Tsukahara syndrome: Evidence for X-linked dominant inheritance and review. American Journal of Medical Genetics Part A 152A (8): 2057–2060.
- ↑ Yiu, E.M., N. Geevasinga, G.A. Nicholson, E.R. Fagan, M.M. Ryan, R.A. Ouvrier (1). A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood. Neurology 76 (5): 461–466.
Sex linkage: X-linked recessive disorders
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