Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Cutaneous Mastocytosis Clinical Trial

Official title:

Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02761473
• Other study ID #: 1608M92621
• Status: Completed
• Start date: November 2016
• Est. completion date: May 1, 2020

Study information

• Verified date: August 2020
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 1, 2020
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months to 23 Years

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous Mastocytosis
• Mastocytosis
• Urticaria
• Urticaria Pigmentosa

Intervention

Other:
• skin biopsy
A skin biopsy will be obtained from a typical UP lesion in affected patients
• blood draw
Blood will be obtained from subjects, parents and unaffected siblings

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

References & Publications (4)

Fett NM, Teng J, Longley BJ. Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations. Am J Dermatopathol. 2013 Feb;35(1):113-6. doi: 10.1097/DAD.0b013e31826330bf. Review. — View Citation

Fried AJ, Akin C. Primary mast cell disorders in children. Curr Allergy Asthma Rep. 2013 Dec;13(6):693-701. doi: 10.1007/s11882-013-0392-6. Review. — View Citation

Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, Matito A, Broesby-Olsen S, Siebenhaar F, Lange M, Niedoszytko M, Castells M, Oude Elberink JNG, Bonadonna P, Zanotti R, Hornick JL, Torrelo A, Grabbe J, Rabenhorst A, Nedoszytko B, — View Citation

Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1609-14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RNA sequencing	Fresh tissue from lesional skin will be obtained for gene expression and mutational analysis	1.5 years
Secondary	SNP microarray analysis	SNP microarray analysis will be performed on DNA obtained from buccal swabs or whole blood samples. Samples from patients and unaffected family members will be compared.	1.5 years