Grupo de Diabetes Monogênico, Unidade de Endocrinologia Genética/Laboratório de Investigação Médica (LIM/25) e Unidade de Diabetes, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Unidade de Endocrinologia Genética, Laboratório de Endocrinologia Celular e Molecular/Laboratório de Investigação Médica (LIM/25), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil; Departamento de Medicina Interna, Divisão de Metabolismo, Endocrinologia e Diabetes, Universidade de Michigan, Ann Arbor, MI, USA.
Arch Endocrinol Metab. 2021 May 18;64(5):559-566. doi: 10.20945/2359-3997000000278.
Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS).
Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed.
An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in and three in . Three large homozygous deletions in were identified by copy-number variant analysis.
Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.
我们旨在使用靶向大规模平行测序（MPS），也称为下一代测序（NGS），建立先天性全身性脂肪营养不良（CGL）的基因诊断。
招募了 9 名具有 CGL 临床诊断的无关个体。我们使用定制的面板来捕获与遗传性脂肪营养不良相关的基因。生成 DNA 文库，使用 Illumina MiSeq 进行测序，并进行生物信息学分析。
对所有 9 名患者均进行了准确的基因诊断。4 名患者在 中存在致病性变异，3 名患者在 中存在致病性变异。通过拷贝数变异分析鉴定出 3 个大的纯合缺失。
尽管我们仅在与 CGL 相关的 2 个基因中发现了等位基因变异，但该面板能够识别不同的变异，包括通过 Sanger 测序可能遗漏的缺失。我们认为 MPS 是一种有价值的工具，可用于包括 CGL 在内的多基因相关疾病的基因诊断。
