MPZ gene codes for making a protein called myelin protein zero, it is found abundant in the myelin sheath, the covering that protects nerves and promotes the efficient transmission of nerve impulses, Schwann cells are the only cells that produces myelin protein zero, This protein is required for the proper formation and maintenance of myelin, it acts like a molecular glue (adhesion molecule) and plays a role in tightly packing the myelin.
Disease:
Mutations in MPZ gene causes disease like Autosomal dominant form of Charcot-Marie-Tooth disease type 1 and other polyneuropathies, More than 100 mutations in MPZ gene causes a form of Charcot-Marie-tooth known as type 1B,These mutations alter the extracellular domain by replacing one of the building blocks (amino acids) in the myelin protein zero with incorrect amino acid, the altered myelin protein zero probably cannot interact properly with other myelin components, which disrupts the formation and maintenance of the myelin sheath, As a result, peripheral nerve cells cannot activate muscles used for movement or relay information from sensory cells back to the brain, causing the signs and symptoms of type 1B Charcot-Marie-Tooth disease.
Chromosome:1 Gene Size: 33197 bp (11962956..11996152)
No Exons:19
Location : 1p36.22
Description:This gene codes for a protein called mitofusin 2,This protein helps to determine the shape and structure of mitochondria during fission and fusion,This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity
Disease :
Mutations in MFN2 gene cause disease like Charcot-Marie-Tooth disease (CMT disease)and Hereditary motor and sensory neuropathy VI,
In Charcot-Marie-Tooth disease Researchers have identified more than 30 MFN2 mutations,Almost all these mutations replace one of the protein building blocks in mitofusin 2 with an incorrect amino acid,As a result the mitofusin 2 protein are altered in critical region and cannot function properly,
Recent research showed that the mutated MFN2 causes mitochondria to form large clusters. In nerve cells these large clusters of mitochondria failed to travel down the axon towards the synapses. It is suggested these mitochondria clots make the synapses fail, resulting in CMT disease
The LMNA gene provides instructions for making several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most of the body's cells. These proteins have a nearly identical sequence of protein building blocks (amino acids). The small difference in the sequence makes lamin A longer than lamin C.The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy,
Disease :
Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome
Mutation in the LMNA gene has been found in most patients with Hutchinson-Gilford progeria syndrome The G608G mutation in exon 11 of the LMNA gene is present in all individuals with HGPS,mutation changes a single DNA building block (nucleotide) in the gene. Specifically, the mutation replaces the nucleotide cytosine with the nucleotide thymine at position, This mutation is also sometimes noted as Gly608Gly or G608G, which refers to the position in the lamin A protein affected by the mutation. The C1824T mutation leads to an abnormal version of the lamin A protein called progerin, which is missing 50 amino acids near one end. The location of this mutation does not affect the production of lamin C. Other mutations in the LMNA gene have been identified in a small number of people with the features of Hutchinson-Gilford progeria syndrome.
The mutations responsible for this disorder result in an abnormal version of lamin A that cannot be processed correctly within the cell. When the altered protein is incorporated into the lamina, it can disrupt the shape of the nuclear envelope. Over time, a buildup of this altered protein appears to damage the structure and function of the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the signs and symptoms of Hutchinson-Gilford progeria syndrome.
