Palmoplantar keratoderma with deafness (Palmoplantar keratoderma With deafness) - Gen GJB2 and MT-TS1.
Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. On the one hand, those affected develop an unusually thick skin on the palms and soles (palmoplantar keratoderma) that begins in childhood. Furthermore, the hearing loss may vary from mild to profound. This hearing loss begins in early childhood and worsens over time. Affected individuals have special difficulty hearing high - pitched sounds.
This process is due to mutations in the GJB2 or MT-TS1 gene.
The GJB2, located on the long arm of chromosome 13 (13q11-q12), encoding the protein binding Gap beta-2, more commonly known as connexin 26. The connexin 26 channels so as to allow the transport of nutrients, ions and molecules signaling between cells. Connexin 26 was found in cells throughout the body, including the inner ear and skin. In the inner ear, consisting of connexin 26 channels are in the cochlea. These channels can help maintain the proper level of potassium ions required for converting sound waves into electrical nerve impulses. This conversion is essential for normal hearing. Moreover, connexin 26 may be involved in the maturation of certain cells of the cochlea. Connexin 26 also plays a role in the growth, maturation and stability of the epidermis. They have identified at least 9 GJB2 gene mutations in people with palmoplantar keratoderma with deafness. These mutations change individual amino acids in the protein connexin 26. altered probably disrupts the function of connexin 26 in normal cells, which may interfere with the function of other connexin proteins. This alteration may affect the growth of skin and affect hearing by altering the conversion of sound waves into nerve impulses.
The MT-TS1 gene, located in mitochondrial DNA, encoding tRNASer (UCN). During assembly of proteins, this molecule binds to a particular amino acid serine (Ser), and inserts it into the appropriate locations growing protein. The tRNASer molecule is present in mitochondria. Through oxidative phosphorylation, mitochondria use oxygen, simple carbohydrates and fatty acids to produce adenosine triphosphate (ATP), the major source of cellular energy. The tRNASer molecule is involved in the assembly of proteins that carry out oxidative phosphorylation. Genetic change MT-TS1, palmoplantar keratoderma associated with deafness replaced with adenine nucleotide guanine nucleotide by the 7445 position in the MT-TS1 (A7445G) gene. This mutation probably disrupts normal molecule encoding tRNASer. As a result, less is available tRNASer (UCN) to assemble proteins within mitochondria. These changes reduce the production of the necessary proteins for oxidative phosphorylation, which can affect the ability of mitochondria to produce ATP. It has not been determined why the effects of mutations in the gene MT-TS1 often limited to cells in the inner ear and skin disease.
Palmoplantar keratoderma with deafness may have different patterns of inheritance. When the disease is due to mutations in the GJB2, it is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. In most cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. Meanwhile, when palmoplantar keratoderma with deafness is caused by mutations in the MT-TS1 gene is inherited in a mitochondrial pattern, also known as maternal inheritance. This pattern of inheritance applies to genes in mitochondrial DNA. Mitochondrial disorders can appear in each generation of a family and can affect both men and women, but men can not pass mitochondrial traits to their children.
Tests in IVAMI: in IVAMI perform detection of mutations associated with palmoplantar keratoderma with deafness, by complete PCR amplification of the exons of GJB2 and MT-TS1, respectively, and subsequent sequencing genes.
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).