Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

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.

• Discordant sibling analysis: Children with UP and their unaffected siblings will be compared to identify germline variants.
• Identical twin and parent analysis: Identical infant twins with a severe UP phenotype will be compared with their unaffected parents.

Inclusion criteria

Affected subject:

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

• Clinical diagnosis of urticaria pigmentosa/cutaneous mastocytosis with representative skin lesions
• Age <23 years
• Capable of giving consent if 18 or older

Inclusion criteria

for Parent:

• Over 16 years of age
• Biologic parent to affected subject
• Capable of providing consent

Inclusion criteria

for Sibling:

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

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Exclusion criteria

• Absence of skin findings representative of classic urticaria pigmentosa
• Patients with primarily systemic mastocytosis
• Unable or unwilling to participate in study procedures

Exclusion criteria

for Parent/Sibling:

• Unable or unwilling to participate in study procedures