SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).
SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).
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DOI：
10.1038/gim.2017.260
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Staufner C
中科院分区：
文献类型：
--
作者：
Lenz D;McClean P;Kansu A;Bonnen PE;Ranucci G;Thiel C;Straub BK;Harting I;Alhaddad B;Dimitrov B;Kotzaeridou U;Wenning D;Iorio R;Himes RW;Kuloğlu Z;Blakely EL;Taylor RW;Meitinger T;Kölker S;Prokisch H;Hoffmann GF;Haack TB;Staufner C
SCYL 1的双等位基因突变最近被鉴定为引起以周围神经病变、小脑萎缩、共济失调和肝功能衰竭的复发为特征的综合征性疾病。先前未确定的婴儿胆汁淤积症或急性肝功能衰竭患者中SCYL 1缺乏症的发生尚未研究;此外，关于肝脏表型知之甚少。我们的目的是在婴儿胆汁淤积症或病因不明的急性肝衰竭患者的外显子组测序研究中识别SCYL 1变异的患者。对成纤维细胞进行深入的临床和生化表型分析以及肝活检和功能研究。来自5个家庭的7名患者与双等位基因SCYL 1变异体进行了鉴定。主要临床表型为复发性低γ-谷氨酰转移酶（GGT）胆汁淤积或急性肝功能衰竭，在婴儿期发病，迟发性神经系统表型可变（CALFAN综合征）。肝危象是由发热性感染引起的，并且是短暂的，但纤维化发展。功能研究强调SCYL 1缺乏与受损的细胞内运输有关。SCYL 1缺乏可导致复发性低GGT胆汁淤积性肝功能障碍，并伴有可变的神经系统表型。像NBAS缺乏症一样，它是引起肝病的细胞内运输先天性疾病的新兴组的成员。
Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype. We aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology. Deep clinical and biochemical phenotyping plus analysis of liver biopsies and functional studies on fibroblasts were performed. Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low γ-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed. Functional studies emphasize that SCYL1 deficiency is linked to impaired intracellular trafficking. SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype. Like NBAS deficiency, it is a member of the emerging group of congenital disorders of intracellular trafficking causing hepatopathy.
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影响因子：
3.3
作者：
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影响因子：
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作者：
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作者：
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通讯作者：
McPherson PS
DOI：
10.1083/jcb.109.1.61
发表时间：
1989-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Yewdell JW