Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations
| Status: | Recruiting |
|---|---|
| Conditions: | Dermatology |
| Therapuetic Areas: | Dermatology / Plastic Surgery |
| Healthy: | No |
| Age Range: | Any - 23 |
| Updated: | 5/3/2018 |
| Start Date: | November 2016 |
| End Date: | December 2018 |
| Contact: | Sheilagh Maguiness, MD |
| Email: | smaguine@umn.edu |
| Phone: | 612-626-8625 |
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.
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.
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.
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
We found this trial at
1
site
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
Click here to add this to my saved trials
