Disease gene identification in non-photosensitive trichothiodystrophy by exome sequencing

Trichothiodystrophy (TTD) is a rare hereditary disorder with symptoms affecting several organs. Brittle hair is the defining feature, which is associated with physical and mental retardation of different severity, skin alterations, proneness to infections and premature aging. Cutaneous photosensitivity is present in about half of the patients and based on this clinical feature a photosensitive and non-photosensitive form of the disease are defined. Photosensitive TTD can be diagnosed by appropriate cellular tests and the causing molecular defects can be detected by analysis of the responsible genes. In contrast, no cellular marker is available for non-photosensitive TTD and the responsible gene is known only in a minority of the cases. Having collected over the years cell samples from non-photosensitive TTD patients we intend to search for the gene(s) defective in the still unsolved patients who represent most of the cases (80-90%). To this purpose we will use the “exome sequencing” technology, a new powerful technology to analyze the sequence of the coding regions (exome) of the genome. The results of this work will provide information on the type and number of the genes responsible for non-photosensitive TTD. The new genes will immediately enable molecular confirmation of the diagnosis in the unsolved cases and will allow identification of the carriers of the molecular defects among the healthy family members. Identification of the molecular defects in cases with different severity of the clinical symptoms could also provide prognostic information.