Abstract：
Whole exome sequencing (WES) provides support for clinical diagnosis and treatment of genetically related diseases based on specific probe capture and high-throughput second-generation sequencing technology. Familial partial lipodystrophy 2 (FPLD2; OMIM # 151660) or type 2 Köbberling-Dunnigan syndrome with insulin resistance syndrome is uncommon in mainland China and elsewhere.
We report the case in order to have a further understanding of FPLD2 or type 2 Kobberling- Dunnigan syndrome) with the assistance of WES and improve the clinical and genetic understanding and diagnosis of this disease.
A 30-year-old woman was admitted to the cadre department of our hospital at 14:00 on July 11, 2021, because of hyperglycemia, a rapid heart rate, and excessive sweating during pregnancy. An oral glucose tolerance test (OGTT) showed that insulin and C-peptide increased slowly after glucose stimulation, and the peak value was extended backward (Table 1). It was suggested that the patient had developed insulin antibodies, resulting in insulin resistance. Her clinical features and familial inheritance were consistent with FPLD2 (type 2 Kobberling-Dunnigan syndrome). The results of WES indicated that a heterozygous mutation occurred in exon 8 of the LMNA gene, because the base C at position 1444 was mutated into T during transcription. This mutation changed the amino acid position 482 of the encoded protein from Arg to Trp. Type 2 Kobberling- Dunnigan syndrome is associated with an LMNA gene mutation. According to the patient\'s clinical manifestations, hypoglycemic and lipid-lowering therapy is recommended.
WES can assist in the simultaneous clinical investigation or confirmation of FPLD2 and help identify diseases with similar clinical phenotypes. This case demonstrates that familial partial lipodystrophy is associated with an LMNA gene mutation on chromosome 1q21-22. This is one of the few cases of familial partial lipodystrophy diagnosed by WES.
We report the case in order to have a further understanding of FPLD2 or type 2 Kobberling- Dunnigan syndrome) with the assistance of WES and improve the clinical and genetic understanding and diagnosis of this disease.
A 30-year-old woman was admitted to the cadre department of our hospital at 14:00 on July 11, 2021, because of hyperglycemia, a rapid heart rate, and excessive sweating during pregnancy. An oral glucose tolerance test (OGTT) showed that insulin and C-peptide increased slowly after glucose stimulation, and the peak value was extended backward (Table 1). It was suggested that the patient had developed insulin antibodies, resulting in insulin resistance. Her clinical features and familial inheritance were consistent with FPLD2 (type 2 Kobberling-Dunnigan syndrome). The results of WES indicated that a heterozygous mutation occurred in exon 8 of the LMNA gene, because the base C at position 1444 was mutated into T during transcription. This mutation changed the amino acid position 482 of the encoded protein from Arg to Trp. Type 2 Kobberling- Dunnigan syndrome is associated with an LMNA gene mutation. According to the patient\'s clinical manifestations, hypoglycemic and lipid-lowering therapy is recommended.
WES can assist in the simultaneous clinical investigation or confirmation of FPLD2 and help identify diseases with similar clinical phenotypes. This case demonstrates that familial partial lipodystrophy is associated with an LMNA gene mutation on chromosome 1q21-22. This is one of the few cases of familial partial lipodystrophy diagnosed by WES.
摘要：
背景：基于特异性探针捕获和高通量第二代测序技术，全外显子组测序（WES）为遗传相关疾病的临床诊断和治疗提供了支持。家族性部分脂肪营养不良2型(FPLD2;OMIM#151660)或2型Köbberling-Dunnigan综合征伴胰岛素抵抗综合征在中国大陆和其他地区并不常见。
目的：我们报告该病例，以便在WES的帮助下进一步了解FPLD2或2型Kobberling-Dunnigan综合征），并提高对该病的临床和遗传学认识和诊断。
方法：2021年7月11日14:00我院干部科收治一名30岁女性，因高血糖，快速的心率，怀孕期间出汗过多。口服葡萄糖耐量试验（OGTT）显示，葡萄糖刺激后胰岛素和C肽缓慢增加，峰值向后扩展(表1)。提示患者出现了胰岛素抗体，导致胰岛素抵抗。她的临床特征和家族遗传与FPLD2（2型Kobberling-Dunnigan综合征）一致。WES结果表明LMNA基因第8外显子发生杂合突变,因为1444位的碱基C在转录过程中突变为T。该突变将编码蛋白质的氨基酸位置482从Arg改变为Trp。2型Kobberling-Dunnigan综合征与LMNA基因突变相关。根据患者的临床表现,推荐降糖降脂治疗。
结论：WES可以帮助同时进行FPLD2的临床研究或确认，并有助于识别具有相似临床表型的疾病。该病例表明家族性部分脂肪营养不良与染色体1q21-22上的LMNA基因突变相关。这是由WES诊断的少数家族性部分脂肪营养不良病例之一。
目的：我们报告该病例，以便在WES的帮助下进一步了解FPLD2或2型Kobberling-Dunnigan综合征），并提高对该病的临床和遗传学认识和诊断。
方法：2021年7月11日14:00我院干部科收治一名30岁女性，因高血糖，快速的心率，怀孕期间出汗过多。口服葡萄糖耐量试验（OGTT）显示，葡萄糖刺激后胰岛素和C肽缓慢增加，峰值向后扩展(表1)。提示患者出现了胰岛素抗体，导致胰岛素抵抗。她的临床特征和家族遗传与FPLD2（2型Kobberling-Dunnigan综合征）一致。WES结果表明LMNA基因第8外显子发生杂合突变,因为1444位的碱基C在转录过程中突变为T。该突变将编码蛋白质的氨基酸位置482从Arg改变为Trp。2型Kobberling-Dunnigan综合征与LMNA基因突变相关。根据患者的临床表现,推荐降糖降脂治疗。
结论：WES可以帮助同时进行FPLD2的临床研究或确认，并有助于识别具有相似临床表型的疾病。该病例表明家族性部分脂肪营养不良与染色体1q21-22上的LMNA基因突变相关。这是由WES诊断的少数家族性部分脂肪营养不良病例之一。
