cutaneous mastocytosis in children: analysis of somatic and germline mutations

Conditions: Urticaria Pigmentosa; Cutaneous Mastocytosis

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.

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.

Eligibility criteria:
inclusion criteria: affected subject: subjects will be eligible to participate in the study if all of the following conditions exist: 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