Frontiers in endocrinology · 2026
Familial partial lipodystrophy type 2 associated with a novel LMNA variant (c.604G>C; p.Glu202Gln): a Colombian family case series.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
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Mendoza Carolina, Cano Raquel, Burgos Luis, Silvera Carlos Arturo
Аннотация
INTRODUCTION: Familial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant laminopathy caused by LMNA gene variants. It is characterized by progressive gluteofemoral lipoatrophy and severe metabolic derangements, including insulin resistance and metabolic dysfunction-associated steatotic liver disease.
METHODS: Three Colombian women (two sisters and a daughter) underwent standardized clinical phenotyping, dual-energy X-ray absorptiometry (DXA), cardiometabolic laboratory testing, and next-generation sequencing-based testing for lipodystrophy-related genes with copy-number variant analysis.
RESULTS: All patients carried the heterozygous LMNA variant c.604G>C (p.Glu202Gln). Patients 1 and 2 exhibited classic Dunnigan phenotypes with diabetes and severe hypertriglyceridemia (up to 1,471 mg/dL), as well as imaging evidence of metabolic dysfunction-associated steatotic liver disease. Patient 3 (age 27) presented an evolving phenotype with central adiposity, clinically reported lower-limb fat loss, and insulin resistance (homeostatic model assessment for insulin resistance [HOMA-IR], 4), without hepatic steatosis on abdominal ultrasound. Management optimization in Patients 1 and 2 using contemporary combination therapy, including glucagon-like peptide-1 receptor agonist-based treatment and sodium-glucose cotransporter-2 inhibitors, was followed by sustained improvement in glycemia (HbA1c 11.1% to 7.6% in Patient 1) and triglycerides. In Patient 3, liraglutide was discontinued due to poor tolerability and limited weight response, and she was transitioned to semaglutide in February 2026.
CONCLUSIONS: This case series expands the phenotypic spectrum of LMNA-associated FPLD2 and supports a disease association for the p.Glu202Gln variant despite its current classification as a variant of uncertain significance. It demonstrates that modern cardiometabolic therapies can be implemented in middle-income settings; however, the absence of functional data, population frequency metrics, and genetic testing in unaffected relatives limits the strength of variant interpretation.
METHODS: Three Colombian women (two sisters and a daughter) underwent standardized clinical phenotyping, dual-energy X-ray absorptiometry (DXA), cardiometabolic laboratory testing, and next-generation sequencing-based testing for lipodystrophy-related genes with copy-number variant analysis.
RESULTS: All patients carried the heterozygous LMNA variant c.604G>C (p.Glu202Gln). Patients 1 and 2 exhibited classic Dunnigan phenotypes with diabetes and severe hypertriglyceridemia (up to 1,471 mg/dL), as well as imaging evidence of metabolic dysfunction-associated steatotic liver disease. Patient 3 (age 27) presented an evolving phenotype with central adiposity, clinically reported lower-limb fat loss, and insulin resistance (homeostatic model assessment for insulin resistance [HOMA-IR], 4), without hepatic steatosis on abdominal ultrasound. Management optimization in Patients 1 and 2 using contemporary combination therapy, including glucagon-like peptide-1 receptor agonist-based treatment and sodium-glucose cotransporter-2 inhibitors, was followed by sustained improvement in glycemia (HbA1c 11.1% to 7.6% in Patient 1) and triglycerides. In Patient 3, liraglutide was discontinued due to poor tolerability and limited weight response, and she was transitioned to semaglutide in February 2026.
CONCLUSIONS: This case series expands the phenotypic spectrum of LMNA-associated FPLD2 and supports a disease association for the p.Glu202Gln variant despite its current classification as a variant of uncertain significance. It demonstrates that modern cardiometabolic therapies can be implemented in middle-income settings; however, the absence of functional data, population frequency metrics, and genetic testing in unaffected relatives limits the strength of variant interpretation.