Clinical and molecular approach of FML. FML: a molecular approach

Familial Multiple Lipomatosis (FML) is an autosomal dominant disorder of hypodermis characterized by the slow growth of encapsulated fatty nodules spread across the trunk and limbs. Middle age adults are commonly affected. Due to its aesthetic features, this disorder may overlap with other dermatological syndromes. The specific etiology has not been identified, therefore, its molecular and biological bases need to be better understood. High-throughput sequencing technologies appear to be a cost-effective tool and have a pivotal role in elucidating different genodermatoses. This study aimed to perform a clinical and molecular characterization of constitutional DNA of seven individuals belonging to five unrelated families diagnosed with FML. Clinical aspects were obtained from medical records and physical examination. The HMGA2 candidate gene was investigated using Sanger sequencing method. Mutational analysis of the genes associated with syndromic lipomatosis AKT1, APC, PIK3CA, MEN-1, and PTEN was performed through Next- Generation Sequencing. In this series, FML was higher among women with 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. Two identical novel variants were found 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.

家族性多发性脂肪瘤病（Familial Multiple Lipomatosis, FML）是一种常染色体显性遗传性皮下组织疾病，以分布于躯干与四肢的包膜脂肪结节缓慢生长为典型特征，好发于中年成人。由于其外观表现具有一定特征性，该疾病易与其他皮肤综合征相混淆。目前其具体病因尚未明确，分子与生物学发病机制仍有待进一步阐明。高通量测序技术作为经济高效的检测手段，在阐明多种遗传性皮肤病的致病机制中发挥关键作用。本研究旨在对5个无亲缘关系家系共7例确诊为FML的患者的胚系基因组DNA开展临床与分子特征分析。临床资料来源于患者的病历记录与体格检查结果。针对候选基因HMGA2，采用桑格测序（Sanger sequencing）进行突变检测；针对与综合征性脂肪瘤病相关的AKT1、APC、PIK3CA、MEN-1及PTEN基因，采用下一代测序（Next-Generation Sequencing, NGS）进行突变分析。本队列研究结果显示，FML在超重且年满30岁的女性中发病率更高，且与胃肠道合并症存在显著关联。活检组织的病理诊断可见脂肪瘤与血管脂肪瘤的典型组织学特征。2名分别来自不同家系的受试者，在HMGA2基因第5外显子中均检出了相同的新发变异；且HMGA2基因第1至4外显子未发现其他序列变异。所有受试者的多基因组合检测结果均未见异常。