Dataset Information

Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With the Mitochondrial MTTK c.8344A>G Variant.

ABSTRACT: Background. Multiple symmetric lipomatosis (MSL), also known as Madelung disease, is a rare adult-onset disorder characterized by benign lipomatosis usually localized to the nuchal and upper thoracic region. A subset of these patients has germline variants in mitochondrial DNA. Methods. Three siblings of Northern European descent with MSL were assessed initially and provided whole blood for DNA analysis. Family history revealed several additional affected siblings who were dispersed across Canada. Targeted histories were obtained from 6 additional affected family members by telephone interviews using a standardized questionnaire, and genomic DNA was obtained from saliva. Sequencing of mitochondrial DNA was performed. Genetic analysis. Eight affected individuals who were studied each had the MTTK gene c.8344A>G variant. None of the affected individuals had epilepsy, ataxia, or myopathy. Conclusion. In this extended Canadian family, the rare MTTK c.8344A>G variant was linked with Madelung disease in multiple family members. Knowing the likely basis of MSL in this family may help with diagnosis, genetic counseling, monitoring for associated phenotypes, and potential future targeted interventions.

SUBMITTER: Perera U

PROVIDER: S-EPMC6166310 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With the Mitochondrial MTTK c.8344A>G Variant.

Perera Uththara U Kennedy Brooke A BA Hegele Robert A RA

Journal of investigative medicine high impact case reports 20180101

Background. Multiple symmetric lipomatosis (MSL), also known as Madelung disease, is a rare adult-onset disorder characterized by benign lipomatosis usually localized to the nuchal and upper thoracic region. A subset of these patients has germline variants in mitochondrial DNA. Methods. Three siblings of Northern European descent with MSL were assessed initially and provided whole blood for DNA analysis. Family history revealed several additional affected siblings who were disperse ...[more]

PMID: 30283804

Similar Datasets

Project description:Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by aberrant multiple and symmetric subcutaneous adipose tissue accumulation in the face, neck, shoulders, back, chest and abdomen, severely affecting the quality of life of patients. At present, precise MSL etiology and pathogenesis remain to be elucidated. The present study first utilized a digital gene expression technique with a next‑generation sequencing platform to profile differentially expressed genes in three cases of MSL vs. normal control tissue. cDNA libraries from these tissue specimens were constructed and DNA sequenced for identification of differentially expressed genes, which underwent bioinformatic analysis using the Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein‑protein interaction (PPI) network analyses. As a result, a total of 859 differentially expressed genes were identified, including 308 upregulated genes (C19orf80, Apelin, C21orf33, FAM166B and HSD11B2 were mostly upregulated 6.984‑, 4.670‑, 4.412‑, 3.693‑ and 3.561‑fold, respectively) and 551 downregulated genes [FosB proto‑oncogene, AP‑1 transcription factor subunit (FOSB), selectin (SEL) E, RAR related orphan receptor (ROR) B, salt inducible kinase (SIK)1 and epidermal growth factor‑like protein (EGFL)6 were mostly downregulated ‑9.845, ‑8.243, ‑8.123, ‑7.702 and ‑7.664 fold, respectively). The GO functional enrichment analysis demonstrated these differentially expressed genes were predominantly involved in biological processes and cellular components, while the KEGG pathway enrichment analysis demonstrated that ribosome, non‑alcoholic fatty liver disease, human T‑lymphotropic virus type 1 (HTLV‑I) infection and Alzheimer's disease pathways were altered in MSL. The PPI network data demonstrated ubiquitin C (UBC), translocator protein (TSPO), Jun Proto‑Oncogene, AP‑1 Transcription Factor (JUN) and FOS were among these differentially expressed genes that participated in regulation of adipocyte differentiation, although no previous study has linked them to MSL. In conclusion, the present study profiled differentially expressed genes in MSL and identified gene pathways that may be associated with MSL development and progression.

Dataset Information

Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With the Mitochondrial MTTK c.8344A>G Variant.

Publications

Multiple Symmetric Lipomatosis (Madelung Disease) in a Large Canadian Family With the Mitochondrial <i>MTTK</i> c.8344A>G Variant.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets