Finding the Causes of Rare Skin Diseases
a better understanding of how the human skin forms and how it functions can be obtained through identifying the genetic causes of various skin disorders. our objective is to identify genes that are critical to skin formation and/or function by identifying the causative genetic changes in individuals or families with uncommon skin disorders.
We will invite any person up to 90 years old that has a genetic skin disorder to participate in this study, as well as any first or second degree family member of a participant that has the genetic skin disorder, whether that family member be affected or unaffected. our goal is to enroll up to 100 distinct families, each with at least 1 affected family member. We will enroll as many family members as possible. each participant will undergo a comprehensive health survey, documentation and photography of their skin lesions, sampling and banking of blood and tissue for Dna, Rna, and cells; all for analysis of loci segregation and sequence variations. We will also enroll up to 40 normal control participants for comparison purposes. Blood and/or tissue samples will be taken from our control group for sampling and banking of blood and tissue for Dna, Rna and cells: all for analysis of loci segregation and sequence variations.
The Dna obtained from blood and from tissue will be used to perform next-generation sequencing (exome sequencing or whole genomic sequencing) in order to identify gene mutations that may be responsible for the affected individual's phenotype. Copy number variation and loss of heterozygosity studies may also be performed to identify chromosomal abnormalities or long areas of chromosomal homozygosity which might help identify regions/genes of interest. Linkage analysis of all the members of the family may be performed in order to narrow down the regions where the potential causative genes may lie.
Rna from blood and tissue may be used to perform experiments whereby the differences in Rna expression between affected and unaffected tissue can be compared (e.g., northern blots, real-time PCR, Rna-seq). Cells may be used to perform in vitro culture and Western blot analyses to identify differences in protein levels between affected and unaffected tissue. Cells may also be used to perform ChiP-seq experiments, where differences in the binding of various transcription factors to regions of Dna will be compared between affected and unaffected tissue.
-male or female subjects up to 90 yrs old who have or have had a skin disorder
-first- or second-degree relatives up to 90 yrs old of an enrolled individual with a skin disorder (i.e. the proband)
-subjects must speak English and/or Spanish.
-subjects must be able to provide written informed consent. Written informed consent will be obtained from the parents or guardians of a participant younger than 18 years of age. Children 10-17 years of age will provide assent as well prior to participation.
-To qualify as normal controls, the individual must be a male or female up to 90 years old, must speak English and/or Spanish, must be able to provide written informed consent, and not have or have had a rare skin disorder. Written informed consent will be obtained from the parents or guardians of a participant younger than 18 years of age.