Then we have the infamous methyl CpG binding protein 2 gene, known far and wide as MeCp2. CpG refers to a nucleotide sequence of cytosine followed by a phosphate group followed by guanine in the 5′ to 3′ direction. What happens during methylization is a methyl group (one carbon and three hydrogen atoms) gets attached to a nucleotide. At a high level the consequences of methylization can be changes in the nucleotide sequence in the DNA which can result in a malformed protein, a silenced gene (no protein produced at all), or, controversially, an activated gene which should have been silent.
The MECp2 gene is on the X chromosome in the q28 region.
The MECp2 protein is abundant in brain cells and present in cells throughout the body.
Some of the consequences of a malfunctioning MECp2 gene are:
- MECp2 duplication syndrome – a portion of the X chromosome is duplicated. This condition is more often found in males. Symptoms are intellectual disability, delayed development (sometimes with retrogression), recurrent respiratory tract infections and seizures. In human females (XX) one X chromosome is typically turned off. If that is the longer version (with duplicated MECp2) then the damage is likely to be less severe. However, one can have skewed X-inactivation where some cells have the normal gene and others have the longer gene. Also known as Lubs X-linked mental retardation syndrome. Some researchers prefer the name Xq28 trisomy.
- MECp2-related severe neonatal encephalopathy is caused by any of at least 19 mutations of the MECp2 gene. This condition almost exclusively affects males and is characterized by small head size (microcephaly), movement disorders, poor muscle tone (hypotonia), breathing problems (including a progressive apnea that eventually requires mechanical ventilation assistance), and seizures. Average life-span – about 2 years.
- Psychoses, Parkinsonism and Mental Retardation X-linked (type 13), usually known as PPM-X syndrome, is almost always found in males and includes mild to severe intellectual disability, bipolar disorder and movement abnormalities (parkinsonism) such as tremors, rigidity and ataxia. In addition, there may be drooling, high palate, abnormal dentition, macrotia (large ears), spasticity, macro-orchidism, microcepahly and micrognathia (small chin). So far, eight particular mutations are responsible for approximately half of all cases of PPM-X syndrome. These mutations either change single protein building blocks or create a premature stop signal.
- X-linked intellectual disability
- some cases once diagnosed as Angelman syndrome
Rett syndrome occurs almost exclusively in females. There are currently more than 620 mutations associated with the Rett syndrome spectrum. Symptoms include severe problems with language and communication, loss of purposeful use of the hands, repeated hand wringing, washing, or clapping motions, slow growth, microcephaly, breathing abnormalities including apnea, spitting or drooling, intense staring, excessive blinking, cold hands and feet, irritability, seizures and scoliosis. https://www.rettsyndrome.org/