Molecular genetic, histologic, immunhistochemical and functional characterization of adipose tissue from patients with Multiple Symmetric Lipomatosis

• Applicants: Dr. Julia Schreml; Professor Dr. Stephan Schreml
• Subject Area: Human Genetics ; Dermatology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 282308098

Multiple Symmetric Lipomatosis (= MSL= Launois-Bensaude disease MIM# 151800) is a rare disorder of the adipose tissue with an estimated incidence of 1:25,000. MSL can be described as regional benign neoplastic growth of the subcutaneous fat tissue. When advanced, the disease almost always becomes mutilating. Possible comorbidities are not well explored. The only effective therapy to date is surgical removal or liposuction. Familial cases displaying autosomal dominant mode of inheritance have been documented. In the past 1 ½ years we have gathered a unique cohort of 25 patients including 4 familial cases. Using exome sequencing in 2 families with multiple affected individuals we were able to identify 2 potentially causative variants. One of the candidates, SHC1 has been extensively studied for its implication in fat cell regulation and especially for its involvement in likely mitochondrially mediated ageing processes (p66 isoform of SHC1). We have isolated and cultivated mesenchymal stem cells from affected and unaffected regions in MSL patients (=human adipose tissue derived stem cells, hASCs). Surpassing our initial goal of exploring the principle method of using primary hASCs to study MSL we have already been able to translate clues from exome sequencing into protein analysis using Western blotting. Results from these experiments present interesting starting points in the understanding of MSL pathogenesis. The combination of clinical assessment as well as histological examination with an array of sophisticated molecular genetic and molecular biology methods is an asset of our proposal. We expect, for the first time, to gain comprehensive insight into the macroscopic, microscopic and molecular phenotype of MSL. Results will be far reaching in the sense that not only they provide the first step towards better diagnostic options for MSL patients but they will likely bring forth new knowledge about basic fat cell biology.

• DFG Programme: Research Grants
• Co-Investigators: Professor Lukas Prantl, Ph.D.; Dr. Sebastian Tschernitz