Potential Impact of Parental Origin of Inheritance on the Clinical Presentation of Familial Partial Lipodystrophy Type 2 Syndrome

Gilio D., Besci Ö., Guidorizzi N. R., Guler M. C., YILDIRIM ŞİMŞİR I., Pelosini C., ...Daha Fazla

CLINICAL ENDOCRINOLOGY, cilt.103, sa.4, ss.504-512, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 103 Sayı: 4
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1111/cen.15303
  • Dergi Adı: CLINICAL ENDOCRINOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, CAB Abstracts, EMBASE, Gender Studies Database
  • Sayfa Sayıları: ss.504-512
  • Anahtar Kelimeler: body composition, dual X-ray absorptiometry, fat mass, lean mass, LMNA, parent-of-origin effect, partial lipodystrophy
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

ContextFamilial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant disorder caused by pathogenic variants in the LMNA gene. The influence of parental inheritance on clinical presentation has not been fully explored.ObjectiveTo investigate the influence of maternal versus paternal inheritance of LMNA variants on the clinical and metabolic phenotype of patients with FPLD2.Design, Patients, MeasurementsThis retrospective cohort study included 83 patients with FPLD2 from four different centres. Clinical, biochemical, and body composition data were analysed. Patients were grouped based on maternal (maternal inheritance group; n = 49) or paternal (paternal inheritance group; n = 34) inheritance of LMNA variants. Statistical comparisons were made between the groups.ResultsPatients in the maternal inheritance group had a younger current age (35 (33) vs. 48 (22) years, p = 0.042) and earlier diagnosis of lipodystrophy (22 (30) vs. 36 (25) years, p = 0.044) compared to those in the paternal inheritance group. Body fat percentages in the arms (23.8 (6.5) % vs. 21.0 (6.2) %, p = 0.034) and trunk (32.1 (10.3) % vs. 28.5 (6.1) %, p = 0.024) were higher in maternal inheritance group. Fatty liver disease (79% vs. 57%, p = 0.029) and pancreatitis (26% vs. 8%, p = 0.033) were more prevalent in paternal inheritance group.ConclusionParental lineage may influence the phenotype of FPLD2: patients with a maternally inherited LMNA variant tend to preserve more adipose tissue in the upper body, while those with a paternally inherited variant experience greater adipose tissue loss in that region, often associated with more severe metabolic complications. These findings highlight the importance of contemplating parental lineage as a relevant factor when evaluating the clinical presentation and management of patients with FPLD2.