Genetic Variants in Linear Localized Scleroderma

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

Detailed Description
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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.

Official Title
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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

Conditions
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Morphea

Intervention / Treatment
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* Other: skin biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: skin biopsy<br>4mm punch biopsy | Other: skin biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |