Fragile X Syndrome ... (Fragile X syndrome) - Gen FMR1

Fragile X syndrome is a genetic process associated with a number of developmental problems, including learning disabilities and cognitive impairment. People usually have delayed development of speech and language that is evident at about 2 years old. Most affected males manifest mild to moderate intellectual disabilities, while about one - third of women affected are people with intellectual disabilities. Children with the syndrome Fragile X may also manifest anxiety and hyperactive behavior such as restlessness or impulsive actions. These individuals may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty concentrating on specific tasks. About one - third of affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. In addition, approximately 15% of men and 5% of women affected have seizures.

Most of the men and half of women with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, jaw and prominent forehead, unusually flexible fingers, flat feet, and the macroorchidism males after puberty.

This process is due to mutations in the FMR1 gene, located on the long arm of chromosome X (Xq27.3). The protein encoded by this gene, FMRP, is expressed in many cell types, but especially in neurons. Their function is still little known, but has been having binding capacity to specific mRNA and is now involved in trafficking mRNA from the nucleus to the cytoplasm.

Over 99% of mutations in FMR1 are expansions of a sequence of three repetitive nucleotide (CGG) in the 5' - untranslated region of the gene before the first exon. Normal alleles the number of repetitions ranges between 6 and between 50-55. In own alleles Fragile X syndrome number of repeats is generally repeated from 200 to over 1,000, causing hypermethylation of this region and the promoter, which lies adjacent, inactivating and causing therefore loss expression of FMRP. However, this mutation is not spontaneous, but evolves over generations, increasing the number of triplet repeats progressively. That is, the full mutations -causantes the fragile syndrome X arise from alleles "premutated" (59 to 200 repetitions of CGG triplet) from the maternal allele transmission (not the case with the transmission of the allele paternal). This process is known as "genetic anticipation".

Less than 1% of all cases of fragile X syndrome is the due to other changes in the FMR1 gene. Mutations can remove part or all of the gene or change one of the amino acids used to encode the FMRP. These genetic changes alter the three dimensional form of the protein or inhibit protein coding. An absence or deficiency of FMRP disrupts the normal functions of nerve cells and, consequently, the nervous system, causing severe learning disabilities, intellectual disabilities, and the other features of fragile X syndrome of.

This process is inherited as a dominant pattern X - linked inheritance is considered dominant because a copy of the altered gene in each cell is sufficient to express the alteration. X - linked dominant means that in women (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to express the process. In males (who have only one X chromosome), a mutation in single copy of a gene in every cell expresses the alteration. In most cases, men have more severe symptoms of the disease than women.

Tests in IVAMI: IVAMI performed in detecting the number of repetitions of the repetitive sequence in the region 5 ' of CGG FMR1 gene in search of full mutations associated with fragile X syndrome of and identifying "premutations" and presence / absence of the sequence AGG possibly related to the predisposition to expansion premutations. To do this, we amplified by PCR with specific primers and then proceed to sequencing amplified.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample). In case of prenatal diagnosis, amniotic fluid or chorionic villi.