Genetic Variants in Linear Localized Scleroderma

Investigation of the Genetic Architecture of Linear Localized Scleroderma (LLS) (Linear Morphea) by Whole Exome Sequencing. A Tailored Approach to Test the Hypothesis That LLS is a Genetic Mosaic Condition

The purpose of this study is to investigate the genetic architecture of Linear Localized Scleroderma (LLS) (linear morphea) by whole exome sequencing.

Study Overview

• Status: Completed
• Conditions: Morphea
• Intervention / Treatment: Other: skin biopsy

Detailed Description

At present the etiology of LLS is unknown, but a genetic background is suspected. Although LLS clearly classifies as a mosaic disorder, its genetics and protein machinery remain to be understood.

We are going to use a tailored approach to identify the genetic factors of LLS. In the first phase of the study we will investigate the genetic architecture in LLS. WES will analyze whole protein coding DNA in skin samples of 50 consenting LLS patient. The aim is to identify the key genes associated with LLS. In the second phase of the study subsequent functional experiments will be performed. Based on the identified candidate genes, knockdown and overexpression models will be created with relevant cell lines (fibroblasts) to identify the biological consequences and confirm the functional relevance of the identified genetic mutations in LLS. Further the protein network active in LLS will be investigated (proteomic analysis).

The described basic genetic studies combined with functional experiments will lay the groundwork for treatment trials to provide possibly novel treatment options.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8032
    • University Children's Hospital, Department of Pediatric Dermatology
  • Zurich, Switzerland, 8091
    • University Hospital, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ≥ 5 years of age with well phenotyped LLS
• Affecting their head and / or face "termed " en coup de sabre " type LLS or Hemiatrophia faciei or Parry-Romberg syndrome, with or without therapy
• Affecting any site of the body except the head or face, with or without therapy

Exclusion Criteria:

• Patients with signs of systemic scleroderma
• Patients with localized scleroderma (morphea) other than the linear type ("plaque-type", "morphea profunda", "generalized morphea") Patients with diagnosed gadolinium induced scleroderma Patients with post-irradiation scleroderma Patients with missing consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: skin biopsy; 4mm punch biopsy	Other: skin biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of key genes /number of mutations in LLS (localized linear scleroderma)	24-30 months

Secondary Outcome Measures

Outcome Measure	Time Frame
the investigation of the protein network of the identified key genes in order to assess their biological function and their relevance in the pathogenesis of LLS.	24-30 months

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Investigators: Principal Investigator: Lisa Weibel, MD, Department Pediatric Dermatology University Children's Hospital Zurich

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): October 31, 2017

Study Registration Dates

• First Submitted: July 21, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (ESTIMATE): August 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Localized
• Other Study ID Numbers: KISPI-UZH-LLS-2014