According to the NICHD, Fragile X syndrome is a genetic disorder that involves alterations in part of the X chromosome. The disorder is a common form of mental retardation in boys. In fragile X syndrome pedigree, the sequence shows signs of variable amplification, its length correlating with the fragile-site expression. The fragile site (at Xq27.3) is unstable microsatellite repeat, denoted as p(CCG)n. There is a direct correlation of increased p(CCG)n number and the degree for instability, meaning that people with large amplifications show somatic variations because of the increased instability.
The disorder was first identified by Julia Bell and J. Purdon Martin in 1943.
Some of the common symptoms include;
- Intellectual disability, delay in crawling, talking and walking;
- Large protruding ears, large testes and flat feet;
- Recurrent otitis media and/or sinusitis during childhood;
- Stereotypical movement like hand flapping;
- General atypical social development signs like problems with memory, shyness and limited eye contact (Fragile X Syndrome NICHD, n.d.).
In 1991, a team of scientists discovered the mutation. They also discovered the gene that causes the syndrome; FMR1 that is called the CGG repeat. It was seen to be abnormally expanded. Generally, the length of the gene ranges from 6-54 copies of CGG with a stable repeat. In humans, it comes about when the permutation form of the repeat has between 50-200 CGG unstable repeat copies. Then, permutation alleles (with >200 CGG repeat copies) expand to the full mutation alleles by transmitting the permutation from the mother to a child (Hagerman, et al., 1996).
According to scientists, the location of the fragile site indicates that Fragile X syndrome is X linked. The alleged gene for the disorder is mutated into two steps: the first mutation causes a permutation while the second mutation converts the permutation to a full mutation that is associated with characteristics of the syndrome. However, conversion from a permutation to a full mutation occurs only when permutation is transmitted from a female carrier. People with the permutation do not show the clinical conditions of Fragile X syndrome (although, females may express premature ovarian failure). Males with full mutation are able to express symptoms of the disorder as they are said to be missing the protein produced by the FMR1 gene. However, due to gene X inactivation, females with a full mutation are less likely to express symptoms of Fragile X syndrome (Hagerman, et al., 1996).
In the pedigree diagram
- A male is given a square symbol while for females it is a circle
- The line between females and males means marriage
- A double line means that they are consanguineous
- Affected individuals are shaded.
Pedigree of X-linked recessive inheritance will show that the affected males are linked through female carriers (with a dot symbol in the circle). Below is a sample of a pedigree diagram (it shows that there is no male to male transmission).
Why Pedigree Diagrams are Useful?
Pedigrees are ancestry records and one can use the charts to help make it clear that ancestry directly affect future generations in different ways. Thus the charts can be used for tracking the family’s genetic disorders and evaluate genetics issues in a certain family tree.
Limitations of Pedigree Diagrams
A pedigree diagram is limited in details of individuals’ direct ancestry which means that there is no space for other relatives (uncles, aunts, brothers, sisters, etc) and as such a person’s other marriages are not recorded. Pedigrees are therefore only valuable if they contain health information instead of just ancestry.
There is no specific treatment for the disorder. That is why educating and training the affected individuals will help them function as best as possible.