skewed X-inactivation, somatic mosaicism.etc). This is due to the variable expressivity of X-linked disorders and the involvement of several mechanisms (e.g. Many female carriers of X-linked 'recessive' disorders demonstrate abnormal phenotype. They are seen only in females and not in males because, in the severe form, they will cause the death of a male embryo, but as females are less severely affected female embryo will survive. X-LINKED DOMINANT LETHALS: These disorders are incompatible with early embryonic survival. Some X-like dominant disorders, such as incontinentia pigmenti (Bloch-Sulzberger syndrome), showed a mosaic pattern of involvement for heterozygous females. examples are Vitamin D resistant (hypophosphatemic) rickets, Charcot-Marie-tooth disease. Affected females can transmit the mutant allele to 50% of his male offspring and 50% of his female offspring. Affected males can transmit the mutant allele to female offspring but not to male offspring. Male and female both are affected, but females are affected in excess and less severely. Hemophilia has been reported in the girl infant with the turner syndrome. (d) A female having only a single X chromosome (Turner syndrome), which is bearing a mutant allele. This pattern has been observed in Duchenne muscular dystrophy. (c) Translocations: If a female is having a translocation involving an autosome and one of the X chromosomes and the translocation disrupts a gene on an X chromosome, in that case, a female might be affected. (b) Homozygosity: When both X chromosomes of females have a mutant allele, as reported in hemophilia A and ichthyosis. It is a possibility that the active X chromosome in the majority of the cells of a heterozygous female is the one having a mutant allele (skewed X inactivation), leading to disorder expression this has been the case in Duchenne muscular dystrophy and hemophilia A. (a) Heterozygosity: X inactivation is a random phenomenon that can involve a mutant allele containing X and a normal allele X in equal proportion in the heterozygous female. This fact is explainable by one of the following possibilities. X-LINKED DISORDERS IN FEMALES: Sometimes, females might be affected by X linked recessive disorders.
Heterozygous female may have a variable expression of X linked recessive disorder due to the random process of X inactivation involving inactivation of the X chromosome with a mutant allele in some cells while inactivation of the X chromosome with a normal allele in other cells (mosaic pattern). VARIABLE EXPRESSION: Heterozygous female are those who are having mutant allele on one X chromosome, and normal allele on another X.
If a carrier female has kids with a healthy male, each male offspring has a 50% chance of being affected, and female offspring have a 50% chance of being a carrier. If an affected male has kids with a healthy female, none of his male offsprings will be affected, but all of his female offspring will be carriers. RISK CALCULATION: The X chromosome from a male is transmitted to daughters, and the Y chromosome is transferred to sons. So from affected males, it can be transmitted to male grandchildren through carrier daughter ('diagonal' or 'Knight's move' transmission). Healthy heterozygous carrier females pass the disorder to affected sons. A male with an affected allele on his single X chromosome is hemizygous and can not transmit the disorder to their male offsprings, but all his daughters would be obligate carriers. Lyon's hypothesis provided an improved understanding of the basic mechanisms responsible for X-linked diseases.Ĭlassically, the descriptions of X-linked inheritance are either X linked recessive and X linked dominant. In 1961, Mary Lyon proposed that in the cells of mammalian females, one X chromosome out of the two would undergo random inactivation in early embryonic life, and therefore, both males and females have a single active X. A 'trait' or 'disorder' determined by a gene on the X chromosome demonstrates X-linked inheritance. There are at least 533 disorders due to the involvement of the genes on the X chromosome. The X chromosome contains 867 identified genes most of these genes are responsible for the development of tissues like bone, neural, blood, hepatic, renal, retina, ears, ear, cardiac, skin, and teeth.
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