Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.
Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.
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DOI：
10.1186/1471-2350-15-32
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发表时间：
2014-03-14
影响因子：
--
通讯作者：
Tavian D
中科院分区：
文献类型：
--
作者：
Missaglia S;Valadares ER;Moro L;Faguntes ED;Quintão Roque R;Giardina B;Tavian D
含α/β-水解酶结构域的蛋白5（ABHD 5）在三酰甘油（TAG）的水解中起重要作用。事实上，ABHD 5是脂肪甘油三酯脂肪酶（ATGL）的共活化剂，其催化TAG水解的初始步骤。ABHD 5基因突变与Chanarin-Dorfman综合征（CDS）的发病有关，CDS是一种罕见的常染色体隐性遗传性脂质储存疾病，以非大疱性先天性鱼鳞病样红皮病（NCIE）、肝肿大和肝脏脂肪变性为特征。我们在这里描述一个5岁的巴西儿童谁提出与NCIE在出生时和弥漫性微小和大泡性脂肪变性的肝活检，因为她是2岁。对ABHD 5基因的编码序列和5′调控区进行了分子生物学分析。一个纯合的新的缺失，影响启动子区和外显子1，被确定，证实了怀疑诊断CDS的这个病人。RT-PCR分析表明，基因组重排完全消除了ABHD 5基因的表达在病人，而只有部分表达的损失，在她的父母被检测到。这是第一份报道描述了ABHD 5基因启动子区的大缺失的鉴定。ABHD 5表达的完全缺失可能解释CDS的早期发病和严重的肝脏受累。分子诊断后，患者开始特殊饮食，脂肪酸含量低，含中链甘油三酯（MCT），尽管存在严重的分子缺陷，但仍显示肝脏和皮肤病学改善。本病例报告扩展了CDS中致病ABHD 5突变的范围，为这种罕见疾病的新致病机制提供了证据。此外，我们的初步数据表明，早期诊断和及时治疗中性脂质积聚可能是有用的CD患者。
α/β-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5′ regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients.
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影响因子：
3.7
作者：
Redaelli C;Coleman RA;Moro L;Dacou-Voutetakis C;Elsayed SM;Prati D;Colli A;Mela D;Colombo R;Tavian D
通讯作者：
Tavian D
影响因子：
9.8
作者：
Lefevre, C;Jobard, F;Fischer, J
通讯作者：
Fischer, J
影响因子：
30.8
作者：
Fischer, Judith;Lefevre, Caroline;Salvayre, Robert
通讯作者：
Salvayre, Robert
影响因子：
11.2
作者：
ANGELINI, C;PHILIPPART, M;LUCKE, S
通讯作者：
LUCKE, S
影响因子：
10.3
作者：
Samuelov, L.;Fuchs-Telem, D.;Sprecher, E.
通讯作者：
Sprecher, E.