MHS : MEF2C Haploinsufficiency Syndrome
The MEF2C gene is the cause of a neuro-genetic disorder characterized by severe intellectual and developmental disability, mutations of this gene have resulted in severe psychomotor retardation, periodic tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features, mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes.Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene.MEF2C is a transcription factor in the Mef2 family.The gene is located at 5q14.3 on the minus (Crick) strand and is 200,723 bases in length. The encoded protein has 473 amino acids with a predicted molecular weight of 51.221 kiloDaltons.
Haploinsufficiency is a mechanism of action to explain a phenotype when a diploid organism has lost one copy of a gene and is left with a single functional copy of that gene. The genotypic state in which one of two copies of a gene is absent is called hemizygosity. (These terms -- hemizygosity and haploinsufficiency -- are not interchangeable; one describes the genotype, while haploinsufficiency provides a potential mechanism to explain the phenotype.) The general assumption is that the single remaining functional copy of the gene cannot provide sufficient gene product (typically a protein) to preserve the wild-type phenotype leading to an altered or even diseased state. As such, hemizygosity is typically transmitted with dominant inheritance, either autosomally or X-linked in female humans.
Dominance describes the circumstance in which both alleles in a diploid organism are present but one allele is responsible for the phenotype. That genotypic state is one of heterozygosity (with two different alleles). Co-Dominance is that situation where the effects of both alleles are apparent in the phenotype.
Haploinsufficiency can occur through a number of ways. A mutation in the gene may have erased the production message. One of the two copies of the gene may be missing due to a deletion. The message or protein produced by the cell may be unstable or degraded by the cell.
A haploinsufficient gene is described as needing both alleles to be functional in order to express the wild type. A mutation is not haploinsufficient, but dominant loss of function mutations are the result of mutations in haploinsufficient genes.