Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant.
Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant.
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2型家族性部分脂肪营养不良的可变表达性和等位基因异质性：p.(Thr528Met) LMNA变异。
DOI：
10.3390/jcm10071497
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发表时间：
2021-04-03
影响因子：
3.9
通讯作者：
Sánchez-Iglesias S
中科院分区：
文献类型：
--
作者：
Araújo-Vilar D;Fernández-Pombo A;Victoria B;Mosquera-Orgueira A;Cobelo-Gómez S;Castro-Pais A;Hermida-Ameijeiras Á;Loidi L;Sánchez-Iglesias S
2型家族性部分脂肪营养不良或邓尼根病是一种以皮下脂肪组织分布异常为特征的代谢紊乱。这种罕见的疾病是由主要影响LMNA基因外显子8和11的变异引起的。在这项研究中，5名FPLD 2诊断患者携带c.1583C>T，p.（Thr528Met）变异，并具有明显的临床异质性。还检测到LMNA和PPARG的特异性多态性。详细记录临床病程、体格检查、生化特征和家族史，沿着通过双能X线吸收测定法评估人体测量特征和身体成分。用含有吡格列酮的经典脂肪分化培养基处理从T528M患者获得的前脂肪细胞。各种脂肪基因进行了评估，通过实时PCR，免疫荧光法用于研究细胞内定位的emerin，核纤层蛋白A及其前体。如油红O染色所示，T528 M患者的前脂肪细胞未能分化，脂肪营养不良患者中各种脂肪形成基因的表达减少，免疫荧光研究显示法尼基化的前核纤层蛋白A在T528 M细胞中积累。我们得出结论，LMNA中的T528M变体可能导致FPLD 2，因为脂肪形成机制受到损害。
Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromised.
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影响因子：
7.1
作者：
MAZESS, RB;BARDEN, HS;HANSON, J
通讯作者：
HANSON, J
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
3.5
作者：
Capanni, C;Mattioli, E;Lattanzi, G
通讯作者：
Lattanzi, G
影响因子：
2.2
作者：
Araújo-Vilar, D;Loidi, L;Cabezas-Cerrato, J
通讯作者：
Cabezas-Cerrato, J
影响因子：
5.8
作者：
Garg, A;Cogulu, O;Agarwal, AK
通讯作者：
Agarwal, AK