Phenotypic and molecular reanalysis of a cohort of patients with monogenic diabetes reveals a case of partial lipodystrophy due to the A8344G mutation in the mitochondrial DNA.

IF 1.6 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Archives of Endocrinology Metabolism Pub Date : 2024-06-19 eCollection Date: 2024-01-01 DOI:10.20945/2359-4292-2023-0084
Pedro Campos Franco, Michelle Patrocinio, Aline Dantas Costa-Riquetto, Augusto Cezar Santomauro, Larissa Garcia Gomes, Milena G Teles
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引用次数: 0

Abstract

Familial partial lipodystrophy (FPLD) is a very rare genetic disease characterized by insulin resistance due to a loss of subcutaneous fat from the extremities together with a progressive storage of fat around the face and neck and inside the abdomen. In over 50% of cases, molecular genetic testing reveals pathogenic variants in two nuclear genes, LMNA and PPARG. The case reported here refers to a woman phenotypically diagnosed with FPLD, who presented with diabetes and multiple cervical lipomatosis and in whom no variant had been found in the nuclear genes classically associated with this syndrome that could explain her phenotype. Genetic sequencing using a target panel containing 48 nuclear genes related to monogenic diabetes plus the whole mitochondrial genome revealed the mitochondrial variant m.A8344G in 84.1% heteroplasmy. Following molecular diagnosis, her phenotype was expanded with the recognition of additional clinical characteristics: mild sensorineural hearing loss, proximal myopathy, fatigue, cognitive impairment, sensory ataxia, cardiac abnormalities and, finally, muscle biopsy findings compatible with mitochondrial disease. Therefore, careful and detailed phenotypic and genotypic reanalysis proved crucial in improving molecular diagnosis in FPLD.

对一组单基因糖尿病患者的表型和分子重新分析发现了一例线粒体 DNA A8344G 突变导致的部分脂肪营养不良病例。
家族性部分脂肪营养不良症(FPLD)是一种非常罕见的遗传病,其特点是由于四肢皮下脂肪减少,胰岛素抵抗,同时面部、颈部和腹部脂肪逐渐囤积。在超过 50% 的病例中,分子基因检测发现了两个核基因 LMNA 和 PPARG 的致病变异。本文报告的病例是一名经表型诊断患有 FPLD 的女性,她伴有糖尿病和多发性宫颈脂肪瘤病,在与该综合征相关的核基因中未发现可解释其表型的变异。使用包含 48 个与单基因糖尿病相关的核基因和整个线粒体基因组的靶向面板进行基因测序,发现了线粒体变异体 m.A8344G,异形率为 84.1%。分子诊断后,她的表型又有了新的临床特征:轻度感音神经性听力损失、近端肌病、疲劳、认知障碍、感觉共济失调、心脏异常,最后,肌肉活检结果与线粒体疾病相符。因此,认真细致的表型和基因型再分析对于改善 FPLD 的分子诊断至关重要。
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来源期刊
Archives of Endocrinology Metabolism
Archives of Endocrinology Metabolism Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.90
自引率
5.90%
发文量
107
审稿时长
7 weeks
期刊介绍: The Archives of Endocrinology and Metabolism - AE&M – is the official journal of the Brazilian Society of Endocrinology and Metabolism - SBEM, which is affiliated with the Brazilian Medical Association. Edited since 1951, the AE&M aims at publishing articles on scientific themes in the basic translational and clinical area of Endocrinology and Metabolism. The printed version AE&M is published in 6 issues/year. The full electronic issue is open access in the SciELO - Scientific Electronic Library Online e at the AE&M site: www.aem-sbem.com. From volume 59 on, the name was changed to Archives of Endocrinology and Metabolism, and it became mandatory for manuscripts to be submitted in English for the online issue. However, for the printed issue it is still optional for the articles to be sent in English or Portuguese. The journal is published six times a year, with one issue every two months.
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