Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

NCT02761473 | Completed

• 1 other identifier: 1608M92621
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Urticaria Pigmentosa; Cutaneous Mastocytosis

Outcome Measures

Primary Outcomes (1)

• RNA sequencing

  Fresh tissue from lesional skin will be obtained for gene expression and mutational analysis

  1.5 years

Secondary Outcomes (1)

• SNP microarray analysis

  1.5 years

Study Arms (2)

Patients with Urticaria Pigmentosa

This group will undergo skin biopsy, blood and buccal swab analyses

Other: skin biopsy; Other: blood draw

Family members of affected patients

This group will undergo blood and buccal swab analyses

Interventions

skin biopsy OTHER

A skin biopsy will be obtained from a typical UP lesion in affected patients

Patients with Urticaria Pigmentosa

blood draw OTHER

Blood will be obtained from subjects, parents and unaffected siblings

Patients with Urticaria Pigmentosa

Eligibility Criteria

• Age: 3 Months - 23 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with urticaria pigmentosa and first degree relatives

You may qualify if:

• 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
• Over 16 years of age
• Biologic parent to affected subject
• Capable of providing consent
• \. Biologic sibling to affected subject 2. Capable of giving consent if 18 or older

You may not qualify if:

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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (4)

• 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, Butterfield JH, Gotlib J, Reiter A, Radia D, Hermine O, Sotlar K, George TI, Kristensen TK, Kluin-Nelemans HC, Yavuz S, Hagglund H, Sperr WR, Schwartz LB, Triggiani M, Maurer M, Nilsson G, Horny HP, Arock M, Orfao A, Metcalfe DD, Akin C, Valent P. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016 Jan;137(1):35-45. doi: 10.1016/j.jaci.2015.08.034. Epub 2015 Oct 21.

  PMID: 26476479 RESULT

• 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. doi: 10.1073/pnas.96.4.1609.

  PMID: 9990072 RESULT

• 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.

  PMID: 24150753 RESULT

• 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.

  PMID: 22892471 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Buccal swabs, skin biopsy and blood

MeSH Terms

Conditions

Urticaria Pigmentosa; Mastocytosis, Cutaneous

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Skin Neoplasms; Neoplasms by Site; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Mast Cell Activation Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: May 4, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: May 1, 2020
• Last Updated: August 20, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)