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At GenPath we offer Fragile X testing as an individual test or as a component of InheriGen Plus.
Methylation polymerase chain reaction enabled high throughput, high resolution, and semiquantitative methylation assessments of FMR1 alleles, as well as determinations of CGG repeat length.
An information-rich CGG repeat primed PCR that detects the full range of fragile X expanded alleles and minimizes the need for southern blot analysis. Chen L, Hadd A, Sah S, Filipovic-Sadic S, Krosting J, Sekinger E, Pan R, Hagerman PJ, Stenzel TT, Tassone F, Latham GJ.
Expansions in the full mutation range are associated with hypermethylation of the FMR1 gene and loss of gene activity. Women who request fragile X carrier screening, regardless of family history, should be offered FMR1 DNA mutation analysis after genetic counseling about the risks, benefits, and limitations of screening. Fragile X syndrome is inherited in an X-linked manner, because the fragile X gene (FMR1) is on the X chromosome.
When a male is a premutation carrier for fragile X syndrome, it usually does not expand to a full mutation when passed on to his daughters. Syndrome, Martin-Bell: Better known as the fragile X syndrome, the most common heritable form of mental retardation.

It can occur in any ethnic group and affects approximately 1 in 3,600 males and 1 in 4,000 – 6,000 females. Females who have between 55-199 CGG repeats in the FMR1 gene are premutation carriers for fragile X syndrome. A male carrier never passes on the fragile X gene to his sons, as he passes on his Y chromosome to his son. While a repeat size in the grey zone has the potential to expand to the premutation range if passed to a child, a repeat size in the grey zone is not expected to expand to a full mutation in one generation. Fragile X syndrome is due to mutation (changes) at the fragile X site and so perforce is X-linked (carried on the X chromosome). Intellectual disability may range from learning disabilities to severe mental retardation and autism.
As a result, this study presents a polymerase chain reaction-based method for comprehensive FMR1 analysis. When a female premutation carrier for fragile X syndrome has children, there is a 50% chance that she will pass her X chromosome with a normal CGG repeat, and a 50% chance she will pass the X chromosome with the premutation. Although it is usually more severe in males than females, the syndrome is due to a dynamic mutation (a trinucleotide repeat) that can change in length and hence in severity from generation to generation, from person to person, and even within a given person.

In addition, the identification of novel methylation mosaic patterns revealed after polymerase chain reaction and capillary electrophoresis may be relevant to several FMR1 disorders. If she passesthe X chromosome with the premutation to a child, it may remain stable, or it may expand, possibly to a full mutation. The fragile X syndrome is known as the Martin-Bell syndrome in honor of their discovery of it in 1943. Symptoms are usually more severe in males than in females, and adult males may exhibit pronounced physical characteristics including enlarged ears and a long face with a prominent chin. In general, the higher the mother’s CGG repeat number, the greater the chance for it to expand to a full mutation in the next generation.

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