ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.
ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.
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DOI：
10.1016/j.ymgmr.2022.100932
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发表时间：
2022-12
影响因子：
1.9
通讯作者：
Ghaloul-Gonzalez, Lina
中科院分区：
文献类型：
--
作者：
Wolfe, Rachel;Heiman, Paige;D'Annibale, Olivia;Karunanidhi, Anuradha;Powers, Alyssa;Mcguire, Marianne;Seminotti, Bianca;Dobrowolski, Steven F.;Reyes-Mugica, Miguel;Torok, Kathryn S.;Mohsen, Al-Walid;Vockley, Jerry;Ghaloul-Gonzalez, Lina
自身免疫性疾病，多系统，面部畸形(ADMFD)是一种常染色体隐性遗传病，由瘙痒基因的致病变异引起。其特征是发育不良、面部畸形、发育迟缓和全身性自身免疫，可表现为自身免疫性肝炎、甲状腺炎和肠病等器官表现。它最初是在10名有血缘关系的旧秩序阿米什患者中描述的，最近在两名英国白人和德国黑人患者中描述。虽然瘙痒蛋白在细胞凋亡和炎症中的作用以前已经被描述过，但在瘙痒缺乏中还没有细胞生物能量学缺陷的报道。在这里，我们提出了一名高加索女性，最初被评估为可能的线粒体呼吸链缺陷，最终被发现有两个新的变种在患者来源的成纤维细胞中缺乏瘙痒蛋白。对患者肌肉的临床研究显示，与对照组相比，线粒体DNA拷贝数为57%。对皮肤成纤维细胞的功能研究显示，线粒体脂肪酸氧化和氧化磷酸化活性降低，总体ATP产量减少。我们的发现证实了一名瘙痒不足患者的线粒体能量障碍，为评估替代治疗方案提供了机会。
Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities. While the role of ITCH protein in apoptosis and inflammation has previously been characterized, a defect in cellular bioenergetics has not yet been reported in ITCH deficiency. Here we present a Caucasian female originally evaluated for possible mitochondrial respiratory chain deficiency, who ultimately was found to have two novel variants in ITCH with absence of ITCH protein in patient derived fibroblasts. Clinical studies of patient muscle showed mitochondrial DNA copy number of 57% compared to controls. Functional studies in skin fibroblasts revealed decreased activity of mitochondrial fatty acid oxidation and oxidative phosphorylation, and decreased overall ATP production. Our findings confirm mitochondrial energy dysfunction in a patient with ITCH deficiency offering the opportunity to assess alternative therapeutic options.
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影响因子：
4.2
作者：
Huemer, Martina;Karall, Daniela;McFarland, Robert
通讯作者：
McFarland, Robert
DOI：
10.1016/j.diff.2017.12.003
发表时间：
2018-01
期刊：
Differentiation; research in biological diversity
影响因子：
--
作者：
Mentrup HL;Hartman A;Thames EL;Basheer WA;Matesic LE
通讯作者：
Matesic LE
影响因子：
3.7
作者：
de Moura MB;Uppala R;Zhang Y;Van Houten B;Goetzman ES
通讯作者：
Goetzman ES
影响因子：
8.8
作者：
Lavie, Julie;De Belvalet, Harmony;Benard, Giovanni
通讯作者：
Benard, Giovanni
影响因子：
2
作者：
Brittain, Helen K.;Feary, Johanna;Wilson, Louise C.
通讯作者：
Wilson, Louise C.