Severe loss of adipose tissue in a Vietnamese lipodystrophy patient caused by LMNA p.G465D mutation: a first clinical characterization and two-year follow-up.

Familial partial lipodystrophy type 2 is the most well-known subtype of lipodystrophy. We describe for the first time the phenotype of a case with lipodystrophy, who carried heterozygous mutation c.G1394A (p.G465D) in the LMNA gene. A 17-year-old girl was diagnosed with FPLD2 due to severe loss of subcutaneous fat in the extremities, buttocks and metabolic complications. However, there was no accumulation of fat over her face and neck, which is remarkably different from the FPLD2 clinical phenotypes. Two years of surveillance showed the challenge due to unable control of insulin resistance, glucose and lipid metabolism. Whole exome sequencing revealed the heterozygous mutation c.1394G>A at exon 11 of LMNA gene (p.G465D). Our case displayed an atypical phenotype of FPLD2 with metabolic anomalies, not cardiovascular diseases. The difficulties of medical management in this case pointed out the urgent need for more effective treatment for individuals suffering from this rare disease.

Vu NP ，Tran HT ，Vu NB ，Ma TTH ，Nguyen TD ，Nong HV ，Nguyen HH ... -  《-》

High-throughput Second-generation Sequencing Technology Assisted Diagnosis of Familial Partial Lipodystrophy (Type 2 Kobberling-Dunnigan Syndrome): A Case Report.

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.

Deng M ，Chen W ，Qi Y 《-》

Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family.

Drac H ，Madej-Pilarczyk A ，Gospodarczyk-Szot K ，Gaweł M ，Kwieciński H ，Hausmanowa-Petrusewicz I ... -  《Neurologia i Neurochirurgia Polska》

The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation.

Wojtanik KM ，Edgemon K ，Viswanadha S ，Lindsey B ，Haluzik M ，Chen W ，Poy G ，Reitman M ，Londos C ... -  《-》

A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy.

Araújo-Vilar D ，Lado-Abeal J ，Palos-Paz F ，Lattanzi G ，Bandín MA ，Bellido D ，Domínguez-Gerpe L ，Calvo C ，Pérez O ，Ramazanova A ，Martínez-Sánchez N ，Victoria B ，Costa-Freitas AT ... -  《-》