Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations
Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations
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患有与 CYP4F22 突变相关的常染色体隐性先天性鱼鳞病的两个兄弟姐妹的形态学改变
DOI：
10.1111/bjd.14860
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发表时间：
2017
影响因子：
10.3
通讯作者：
Hennies HC
中科院分区：
文献类型：
--
作者：
Gruber R;Rainer G;Weiss A;Udvardi A;Thiele H;Eckl KM;Schupart R;Nürnberg P;Zschocke J;Schmuth M;Volc-Platzer B;Hennies HC
由CYP 4F 22基因突变引起的常染色体隐性遗传先天性鱼鳞病（autosomalrecessivecongenitalichthyosis，ARCI）非常罕见。CyP 4F 22是细胞色素P450家族4的一种蛋白质，编码一种决定酰基神经酰胺形成的表皮ω-羟化酶，推测其对皮肤屏障功能至关重要。我们报告一个女孩的近亲父母提出了胶棉婴儿挛缩的大关节和掌跖超线性。在疾病的过程中，她开发了精细的皮肤鳞屑与红皮病，后者消失，直到6个月的年龄。她的妹妹表现出一种广泛的精细缩放表型，有趣的是，她出生时没有胶棉膜。使用新设计的皮肤遗传学基因组对所有已知的ARCI候选基因进行分析，并采用新一代测序方法，结果显示两名女孩的CYP 4F 22中存在一个先前未知的纯合剪接位点突变c.549+5G>C，证实了ARCI的诊断。透射电子显微镜的超微结构分析表明，在这两个病人表皮增生，orthoderatosis与持久性的corneodesmosomes进入外角质层层，破碎和紊乱的层状脂质双层，这可能是由于不均匀的板层体分泌，以及板层体和脂质嵌入角质细胞。这些发现与功能水平上的经表皮水分丢失增加相关。我们首次在超微结构和功能水平上报告了CyP 4F 22缺陷表皮中的火棉胶婴儿表型和表皮屏障损伤，并证实了CyP 4F 22对表皮成熟和屏障功能的重要性。
Autosomal recessive congenital ichthyosis (ARCI) caused by mutations inCYP4F22is very rare. CyP4F22, a protein of the cytochrome‐P450 family 4, encodes an epidermal ω‐hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin‐barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine‐scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next‐generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice‐site mutation c.549+5G>C inCYP4F22in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22‐deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.
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影响因子：
6.5
作者：
Eckl, Katja-Martina;Tidhar, Rotem;Hennies, Hans C.
通讯作者：
Hennies, Hans C.
影响因子：
3
作者：
J. Lugassy;H. Hennies;M. Indelman;Z. Khamaysi;R. Bergman;E. Sprecher
通讯作者：
E. Sprecher
影响因子：
9.8
作者：
Aldahmesh, Mohammed A.;Mohamed, Jawahir Y.;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.
土耳其板层状鱼鳞病患者队列的基因型和眼前节表型
影响因子：
1.2
作者：
M. Palamar;H. Onay;İ. Ertam;E. Ateş;T. Dereli;F. Ozkinay;A. Yağcı
通讯作者：
A. Yağcı