High-throughput Second-generation Sequencing Technology Assisted Diagnosis of Familial Partial Lipodystrophy (Type 2...

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.