As with all medical conditions, there may be many causal factors. Further relevant information on causes of X Chromosome Disorders may be found in:
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Fragile X syndrome is an X-linked condition that doesn't follow a simple X-linked inheritance pattern. The normal sequence of the FMR1 gene was identified at Xq27.3 in 1991. The unique mutation that results in fragile X syndrome consists of an expanding region of a specific triplet of nitrogenous bases: cytosine, guanine, guanine (CGG) within the gene's deoxyribonucleic acid (DNA) sequence. Normally, FMR1 contains 6 to 50 sequential copies of the CGG triplet. When the number of CGG triplets expands to the range of 50 to 200 repeats, the region of DNA becomes unstable and is referred to as a premutation. A full mutation consists of over 200 CGG triplet repeats.
The full mutation typically causes abnormal methylation (methyl groups attach to components of the gene) of FMR1. Methylation inhibits gene transcription and thus protein production. The reduced or absent protein product (FNIRP) is responsible for the clinical features of fragile X syndrome. Approximately 15% to 20% of males with a full mutation don't have fragile X. This may be explained by either the ability of unmethylated portions (of their mutated FMR1) to be transcribed for eventual protein production, or that these males are mosaic for the FMR1 premutation. In asymptomatic mosaic males it's believed that the cells with a premutation can produce enough protein to compensate for the cells that contain a full mutation and consequently produce no protein.
Approximately 50% of females who inherit a full mutation from their mother have clinical features of fragile X syndrome. This is primarily due to the normal process of random X inactivation. At the time of meiosis, both X chromosomes must be activated. However, shortly after the zygote stage, an X chromosome is inactivated in every cell. Clinically measurable effects of the full FMR1 mutation will be more likely in relevant tissues or organs that have a disproportionate number of cells in which the normal X chromosome has been inactivated.
Males with a premutation don't have fragile X. They're considered unaffected or normal-transmitting males. Because males have only one X chromosome, all daughters of a transmitting male will inherit their father's X chromosome with the premutation. None of the male's sons will inherit the premutation because they inherit their father's Y chromosome rather than the X chromosome.
Females with the premutation don't have fragile X syndrome. However, the premutation can expand into the full mutation range (>200 CGG triplets) when it's transmitted from a premutation carrier mother to her offspring. This expansion can occur during or after maternal meiosis. Therefore, the following possibilities exist for every pregnancy of a mother with a premutation.
❑ A female conceptus receives the mother's X chromosome with the nonmutated FMR1 gene. She won't be affected with fragile X. None of her future offspring will be at risk for inheriting the syndrome from her.
❑ A male conceptus receives the mother's X with the nonmutated FMR1 gene. He won't be affected with fragile X. None of his future offspring will be at risk for inheriting the syndrome from him.
❑ A female conceptus receives the mother's X chromosome with the FMR1 premutation. She'll be a carrier like her mother but won't have fragile X syndrome. Her future offspring will be at risk for inheriting a full mutation from her.
❑ A male conceptus receives the mother's X with the FMR1 premutation. He won't be affected with fragile X. All of his future daughters but none of his future sons will inherit the premutation from him.
❑ A female conceptus receives the mother's X chromosome with the FMR1 gene whose premutation expanded into a full mutation during or after maternal meiosis. Depending on the outcome of random X inactivation, the daughter may have clinically definable fragile X syndrome. Her future offspring will be at risk for inheriting the full mutation and, thus, the syndrome from her.
❑ A male conceptus receives the mother's X chromosome with the FMR1 gene whose premutation has expanded into a full mutation during or after maternal meiosis. In 85% of cases, the son in this situation will have fragile X syndrome. Evidence indicates, however, that the FMR1 gene in the son's gametes will have the CGG triplet repeat within the premutation range, not the full mutation range like his somatic cells. Therefore, his future daughters wouldn't be expected to have fragile X syndrome.
It should be noted that most commonly the FMR1 status of a mother is subsequently determined after her son is clinically and later molecularly diagnosed with fragile X syndrome. Health care professionals need to be sensitive to the fact that the mother could either find out she's a carrier of a premutation or she has a full mutation. Consequently, not only will she learn her son's diagnosis but she, herself, could be diagnosed with fragile X if she has a full mutation and clinical symptoms.
Fragile X syndrome is estimated to occur in about 1 in 1,500 males and 1 in 2,500 females. It has been reported in almost all races and ethnic populations.
Source: Professional Guide to Diseases (Eighth Edition), 2005
In this disease, B cells and B-cell precursors may be present in the bone marrow and peripheral blood, but a mutation in the B-cell protein tyrosine kinase causes failure of the B cells to mature and to secrete immunoglobulin. In the absence of protective immunoglobulins, the affected individual develops repeated infections. Worldwide, malnutrition is the primary cause of antibody disorders.
Humoral immune deficiencies account for 50% of all primary immunodeficiencies. IgA deficiency is the most common antibody deficiency symdrome, followed by common variable immunodeficiency (CVID). The incidence of these two disorders is 1 in 700 persons.Selective IgM deficiency is rare. IgG4 deficiency occurs in 10% to 15% of the population.
Source: Professional Guide to Diseases (Eighth Edition), 2005
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