Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy
Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy
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DOI：
10.1016/j.metabol.2017.04.010
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发表时间：
2017-07-01
影响因子：
9.8
通讯作者：
Oral, Elif Arioglu
中科院分区：
文献类型：
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作者：
Akinci, Baris;Onay, Huseyin;Oral, Elif Arioglu
客观的。家族性部分脂肪营养不良（FPLD）是一种罕见的遗传性疾病，其特征是皮下脂肪部分缺乏。这项多中心前瞻性观察研究包括 56 名 FPLD 受试者（18 个独立的土耳其家庭）的数据。招募三十名健康对照者进行比较。结果。在 9 个家族中确定了 LMNA 基因的致病变异。其中，在四个家族中鉴定出典型的外显子 8 密码子 482 致病变异。对LMNA基因的分析还揭示了外显子1密码子47、外显子5密码子306、外显子6密码子349、外显子9密码子528和外显子11密码子582致病变异。 PPARG基因分析揭示了两个家系的外显子3 p.Y151C致病性变异和1个家系的外显子7 p.H477L致病性变异。在另一个家族中检测到 LMNB2 基因的非致病性外显子 5 p.R215Q 变体。另外五个家族的任何基因测序均未发现突变。 MRI 研究显示，具有不同点突变的受试者之间的脂肪分布模式略有不同，尽管在具有 LMNA p.R349W 致病性变异的受试者中存在显着差异。与具有 LMNA 基因致病性变异的受试者相比，具有 PPARG 基因致病性变异的受试者的脂肪减少不显着，瘦素水平相对较高。在所有受试者中均检测到与胰岛素抵抗相关的各种代谢异常。观察终末器官并发症。结论。我们在土耳其 FPLD 患者的 LMNA 和 PPARG 基因中发现了分散的各种致病变异。与错义突变位点相关的 LMNA 致病性变异患者的表型异质性非常显着。 FPLD 由 LMNA 或 PPARG 的致病性变异引起，与胰岛素抵抗相关的代谢异常有关，从而导致发病率增加。 (C) 2017 Elsevier Inc. 保留所有权利。
Objective. Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat.Methods. This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison.Results. Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Qvariant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed.Conclusion. We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity. (C) 2017 Elsevier Inc. All rights reserved.