Division of Endocrinology, Paulista School of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo, 04039-032 São Paulo, São Paulo, Brazil.
Eur J Endocrinol. 2012 Sep;167(3):423-31. doi: 10.1530/EJE-12-0268. Epub 2012 Jun 14.
Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy.
We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.
ALL PATIENTS WITH TYPICAL FPLD WERE FOUND TO CARRY LMNA MUTATIONS: seven patients harbored the heterozygous p.R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045C>T) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1.
We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy.
LMNA 基因突变与多种称为层粘连蛋白病的疾病有关，这些疾病表现出异质性表型，包括影响肌肉、轴突神经元、早老综合征和脂肪营养不良的疾病。在脂肪营养不良中，LMNA 突变在具有 Dunnigan 型家族性部分脂肪营养不良（FPLD）的患者中最常被报道；然而，在体脂丧失模式方面观察到表型异质性。在这项研究中，我们在各种形式的脂肪营养不良患者中寻找 LMNA 突变。
我们研究了 21 名无关的脂肪营养不良患者。受试者接受了完整的临床评估，并分为典型 FPLD（n=12）、非典型部分脂肪营养不良（n=7）或全身性脂肪营养不良（n=2）。对 LMNA 基因进行分子分析，通过双能 X 射线吸收法分析体脂肪，并进行生化测量。
所有典型 FPLD 患者均携带 LMNA 突变：7 名患者携带杂合子 p.R482W（c.1444C>T），2 名患者携带 p.R482Q（c.1445G>A），2 名个体携带新的杂合子变异 p.N466D（c.1396A>G），均在 8 号外显子中。此外，在 11 号外显子中还发现了纯合子 p.R584H（c.1751 G>A）突变。在非典型部分脂肪营养不良患者中，有 2 名患者携带 LMNA 突变：11 号外显子中的新杂合子 p.R582C 变异（c.1744 C>T）和 6 号外显子中的杂合子替换 p.R349W（c.1045C>T）。在全身性脂肪营养不良患者中，只有 1 名患者携带 LMNA 突变，即 1 号外显子中的杂合子 p.T10I（c.29C>T）。
我们在表型多样化的脂肪营养不良中发现了 LMNA 突变。此外，我们的研究拓宽了脂肪营养不良中 LMNA 突变的谱。
