Fragile X Syndrome
Introduction
Introduction The fragile X chromosome means that the chromosomes between the Xq27 and Xq28 bands are filament-like, resulting in a connected body-like structure at the end. This filament-like part is prone to breakage. Therefore, it is called fragile site. The X chromosome having a fragile site at Xq27 is called fragile Xchromosome, abbreviated as fra(x), and the resulting disease is called fragile X syndrome (OMIM309550). A large amount of data indicates that the incidence of fra(x) accounts for about 1/2 to 1/3 of patients with X-linked intelligent hypoplasia. In the general male population, the detection rate is 1.8/1000. Its incidence is second only to the congenital type (Down's syndrome).
Cause
Cause
The reason for this is due to the 5' untranslated region of the fragile X mental retardation gene (FMR1), the genetically unstable (CGG) n trinucleotide repeat, (CGG)n is about 8 to 50 copies in normal people, but Normal male transmitters and female carriers increased to 52-200 copies, while adjacent CpG islands were not methylated, known as premutation. The former mutant had no or only mild symptoms. The CGG region of female carriers is unstable, and the copy number is increasing from generation to generation (ie, dynamic mutation) during the transmission to the offspring, so that in male patients and women with high expression in fragile sites, the number of CGG repeats reaches 200-1000 copies, adjacent. The CpG island is also methylated and is called fullmutation. Almost all patients do not express or have only low expression of FMR1 mRNA, resulting in clinical symptoms. This is one of the typical diseases of dynamic mutation.
Another dynamic mutation of the FMR2 gene located in Xq28 results in fragile E mental retardation, which is associated with the GCC repeat of the 5' non-coding region of the gene. The normal repeat number is 7-35, the pre-mutation is 130-150, and the total mutation is 230 to 750.
Examine
an examination
Related inspection
Karyotype analysis
A diagnosis can be made based on the typical clinical symptoms of the disease. The diagnosis of fragile X syndrome can be made using karyotype analysis. The detection rate of the fragile X chromosome is affected by the composition and time of the medium. Removal of folic acid from the culture medium or addition of a mutagen is advantageous for detection. The detection rate of female heterozygotes decreased with age. Accurate genetic diagnosis and prenatal genetic diagnosis of fragile X syndrome can be performed by Southern hybridization or amplified fragment length polymorphism (AFLP). The specific antibody of the FMR1 gene-encoded protein detects the FMRP protein and is also a common method for the diagnosis of fragile X syndrome.
Diagnosis
Differential diagnosis
A diagnosis can be made based on the typical clinical symptoms of the disease. The diagnosis of fragile X syndrome can be made using karyotype analysis. The detection rate of the fragile X chromosome is affected by the composition and time of the medium. Removal of folic acid from the culture medium or addition of a mutagen is advantageous for detection. The detection rate of female heterozygotes decreased with age. Accurate genetic diagnosis and prenatal genetic diagnosis of fragile X syndrome can be performed by Southern hybridization or amplified fragment length polymorphism (AFLP). The specific antibody of the FMR1 gene-encoded protein detects the FMRP protein and is also a common method for the diagnosis of fragile X syndrome.
