<p>Clinical and Molecular Investigation of Familial Multiple Lipomatosis: Variants in the <em>HMGA2</em> Gene</p>

Abstract

Background: Familial multiple lipomatosis (FML) is an autosomal dominant disorder characterized by the slow growth of encapsulated nodules spread across the trunk and limbs. Currently, there is no specific etiology; therefore, its molecular and biological bases need to be better understood. High-throughput sequencing technologies appear to be a costeffective tool and have a pivotal role in elucidating different genodermatoses.Objective: This study aimed to perform a clinical and molecular characterization of constitutional DNA of seven individuals belonging to five unrelated families diagnosed with FML. Patients and methods: Clinical aspects were obtained from medical records and physical examination. HMGA2 gene was investigated using Sanger sequencing method. Mutational analysis of other genes associated with syndromic lipomatosis AKT1, APC, PIK3CA, MEN-1, and PTEN was performed through next-generation sequencing. Results: In this series, FML was predominant among women who were overweight and reaching the age of thirty and was associated with gastrointestinal comorbidity. Histopathological diagnosis of biopsies revealed typical features of both lipoma and angiolipoma. We identified two identical novel variants with unknown significance in exon 5 of the HMGA2 gene in two participants of different families. There were no additional changes in exons 1 to 4 of the HMGA2 gene. Multi-gene panel was normal in all cases. Conclusion: Variants found in exon 5 of the HMGA2 gene have not been described and have an uncertain significance in the genesis of FML. Further studies, including a more significant number of affected individuals and functional analysis of the novel variants of HGMA2 gene, should be undertaken to better understand its biological role in FML.

A rare case of a giant retroperitoneal lipoma with multiple limb and trunk lipomata without familial multiple lipomatosis

“…Due to the rarity of giant retroperitoneal lipoma, and the presence of multiple limb lipomata, HMGA2 gene testing was undertaken to assess for familial multiple lipomatosis, which is a rare disease characterized by multiple lipomas of the trunk and limbs. Its underlying genetic cause is unknown, although literature suggests deregulation of the HMGA2 gene which encodes for aberrant cell proliferation and development of benign tumours may be responsible [ 11 ]. Despite him having multiple superficial lipomas, his testing was negative.…”

Laplacian Likelihood-Based Generalized Additive Model for RNA-Seq Analysis of Oral Squamous Cell Carcinoma

“…Learning of the gene knock-out in mouse for this gene has shown that it has a role in obesity due to diet. The HMGA2 gene-related disorders include Pleomorphic Syndrome, Salivary Adenoma and Silver-Russell Syndrome (Granados et al, 2020).…”

Rare Forms of Lipomatosis: Dercum’s Disease and Roch-Leri Mesosomatous Lipomatosis

“…Autosomal dominant inheritance has been reported but the penetrance is variable within the same family. Abnormalities of the 12q13-15 region, which contains the HMGA2 gene and PALB2 gene mutation, have been reported [ 49 ].…”