Trichothiodystrophy (trichothiodystrophy) - Genes ERCC2, ERCC3, GTF2H5 and MPLKIP.

Trichothiodystrophy (TTD) is a rare inherited disease that affects many parts of the body, characterized by sparse and brittle hair that breaks easily due to lack of sulfur.

Signs and symptoms of the disorder vary widely. Mild cases may involve only the hair. More severe cases can also cause developmental delay, intellectual disability and recurrent infections. In these cases, affected individuals may survive only in infancy or early childhood. Other features of trichothiodystrophy may include ichthyosis, nail abnormalities of the hands and feet, congenital cataract, motor incoordination and skeletal abnormalities. About half of all people with the disease are extremely sensitive to ultraviolet rays from sunlight (UV). These people develop a severe sunburn after spending only a few minutes in the sun. However, for reasons that are unclear, they do not develop other sun - related problems such as excessive hipercrómicas skin blemishes or an increased risk of skin cancer. Trichothiodystrophy many people say they do not sweat. Mothers of children with trichothiodystrophy can present problems during pregnancy, including preeclampsia and HELLP syndrome called that can damage the liver. Trichothiodystrophy fetuses are at increased risk of preterm birth, low birth weight and slow growth.

This disease is due to mutations in genes ERCC2, located on the long arm of chromosome 19 (19q13.3); ERCC3, located on the long arm of chromosome 2 (2q21); GTF2H5, located on the long arm of chromosome 6 (6q25.3) and MPLKIP, d the short arm of chromosome 7 (7p14.1).

The proteins encoded by these genes function together as part of the complex group of proteins corrsponden to general transcription factors IIH (TFIIH). This complex is involved in the repair of DNA damage that can be caused by UV radiation. The TFIIH complex also plays a role in gene transcription, which is the first step in protein synthesis.

Have identified at least 20 ERCC2 gene mutations, a mutation in the gene ERCC3, three mutations in the gene GTF2H5 and 8 mutations in the gene MPLKIP, causing trichothiodystrophy. Mutations in ERCC2, ERCC3, GTF2H5 genes or reduce the amount of TFIIH complex within the cells, which impairs both DNA repair, such as gene transcription. An inability to repair DNA damage probably underlies sun sensitivity in affected individuals. Studies suggest that many of the other features of trichothiodystrophy can lead to problems with the transcription of genes required for normal development before and after birth. Mutations have been identified in at least one gene, MPLKIP, causing a non - photosensitive form of trichothiodystrophy. Little is known about the protein produced from the gene MPLKIP, although there seems to be involved in DNA repair. It is unclear how mutations in the gene result MPLKIP various features of trichothiodystrophy. In some cases, the genetic cause is unknown trichothiodystrophy.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with trichothiodystrophy, by complete PCR amplification of the exons of the ERCC2, ERCC3, GTF2H5 and MPLKIP genes, respectively, and subsequent sequencing.

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).