Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Brief Title

Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Official Title

Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Brief 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.

Study Type


Primary Outcome

RNA sequencing

Secondary Outcome

 SNP microarray analysis


Urticaria Pigmentosa


skin biopsy

Study Arms / Comparison Groups

 Patients with Urticaria Pigmentosa
Description:  This group will undergo skin biopsy, blood and buccal swab analyses


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

November 2016

Completion Date

May 1, 2020

Primary Completion Date

October 1, 2019

Eligibility Criteria

        Inclusion Criteria:

        Affected subject:

        Subjects will be eligible to participate in the study if all of the following conditions

          1. Clinical diagnosis of urticaria pigmentosa/cutaneous mastocytosis with representative
             skin lesions

          2. Age <23 years

          3. Capable of giving consent if 18 or older

        Inclusion Criteria for Parent:

          1. Over 16 years of age

          2. Biologic parent to affected subject

          3. Capable of providing consent

        Inclusion Criteria for Sibling:

        1. Biologic sibling to affected subject 2. Capable of giving consent if 18 or older


        Exclusion Criteria:

          1. Absence of skin findings representative of classic urticaria pigmentosa

          2. Patients with primarily systemic mastocytosis

          3. Unable or unwilling to participate in study procedures

        Exclusion Criteria for Parent/Sibling:

        1. Unable or unwilling to participate in study procedures




3 Months - 23 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


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Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

University of Minnesota

Study Sponsor

, , 

Verification Date

August 2020