Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations
Condition: Urticaria Pigmentosa; Cutaneous Mastocytosis
MeSH terms: Mastocytosis; Mastocytosis, Cutaneous; Mastocytoma; Urticaria Pigmentosa; Urticaria
Study type: Observational

Summary: 
      Pediatric mastocytosis is an orphan disease, which encompasses several clinically distinct
      entities including solitary mastocytoma, urticaria pigmentosa, diffuse cutaneous mastocytosis
      and the newly recognized mast cell activation syndrome. The most common form of pediatric
      mastocytosis is cutaneous maculopapular mastocytosis (CMPM), also known as urticaria
      pigmentosa (UP). There are significant knowledge gaps regarding the genetic basis of
      pediatric mastocytosis and the functional activity of mast cells in this condition. The
      Pediatric Dermatology and Pediatric Oncology services at the University of Minnesota Masonic
      Children's Hospital are seeing significant growth in clinical volumes of pediatric
      mastocytosis, including rare, familial cases. The aims of this study are to prospectively
      explore germline risk for UP and to perform a mutational analysis to identify somatic
      mutations, beyond those currently identified, in pediatric patients with UP.
    

Detailed description: 
      Urticaria pigmentosa (UP) is a relatively common disorder in pediatric patients, and little
      is known regarding the somatic and germline genetic variants associated with the disease. The
      University of Minnesota Masonic Children's Hospital is a regional referral center for
      pediatric patients with mast cell disorders. Collaborators on this study include several
      University departments including: Pediatric Dermatology, Pediatric Oncology, the Biomedical
      Genomics program, Lab Medicine and Pathology department. We hypothesize that because of
      differences observed in the clinical behavior of pediatric- and adult-onset mast cell
      disease, specifically UP, we will identify novel somatic gene variants in addition to c-KIT .
      We further hypothesize that we will observe novel germline genetic variants in pediatric UP
      distinct from what has previously been described in adults.

      Specific Aims include the following:

      Specific Aim 1: RNA Sequencing for Gene Expression and Mutation Analysis. Utilizing RNA
      sequencing (RNA-Seq), we will perform paired lesional and peripheral blood sequencing in UP
      cases to identify variation in gene expression and define novel somatic mutations associated
      with pediatric UP.

      Specific Aim 2: Exploration of Germline Risk. Utilizing single nucleotide polymorphism (SNP)
      array, we will perform linkage analysis in UP cases and their unaffected family members to
      identify germline genetic variants associated with UP.

        1. Discordant sibling analysis: Children with UP and their unaffected siblings will be
           compared to identify germline variants.

        2. Identical twin and parent analysis: Identical infant twins with a severe UP phenotype
           will be compared with their unaffected parents.
    

Intervention name(s): skin biopsy; blood draw
Intervention type(s): Other; Other
Intervention description(s): A skin biopsy will be obtained from a typical UP lesion in affected patients; Blood will be obtained from subjects, parents and unaffected siblings
Observational model: Family-Based
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with urticaria pigmentosa and first degree relatives
      
Biospecimen description: 
      Buccal swabs, skin biopsy and blood