Targeted regions sequencing identified four novel <i>PNPLA1</i> mutations in two Chinese families with autosomal recessive congenital ichthyosis

Li, Liangshan; Liu, Wenmiao; Xu, Yinglei; Li, Miaomiao; Tang, Qian; Yu, Bo; Cai, Renmei; Liu, Shiguo

doi:10.1002/mgg3.1076

Cited by 4 publications

(2 citation statements)

References 22 publications

(31 reference statements)

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“…The results suggest that the pathogenesis of AD may be due to a reduction in the combination of esterified ω-hydroxy FAs (EO) and sphingosine (S) (EOS) synthesis and insufficient CLE formation ( 112 ). Since the frequency of PNPLA1 gene mutations among ARCI patients is rather low, there are no sufficient data yet to define a correlation between the genotype and the type of skin lesions ( 113 ).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Zwara

Wertheim–Tysarowska²,

Mika

2021

Front. Med.

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The skin is a flexible organ that forms a barrier between the environment and the body's interior; it is involved in the immune response, in protection and regulation, and is a dynamic environment in which skin lipids play an important role in maintaining homeostasis. The different layers of the skin differ in both the composition and amount of lipids. The epidermis displays the best characteristics in this respect. The main lipids in this layer are cholesterol, fatty acids (FAs) and ceramides. FAs can occur in free form and as components of complex molecules. The most poorly characterized FAs are very long-chain fatty acids (VLCFAs) and ultra long-chain fatty acids (ULCFAs). VLCFAs and ULCFAs are among the main components of ceramides and are part of the free fatty acid (FFA) fraction. They are most abundant in the brain, liver, kidneys, and skin. VLCFAs and ULCFAs are responsible for the rigidity and impermeability of membranes, forming the mechanically and chemically strong outer layer of cell membranes. Any changes in the composition and length of the carbon chains of FAs result in a change in their melting point and therefore a change in membrane permeability. One of the factors causing a decrease in the amount of VLCFAs and ULCFAs is an improper diet. Another much more important factor is mutations in the genes which code proteins involved in the metabolism of VLCFAs and ULCFAs—regarding their elongation, their attachment to ceramides and their transformation. These mutations have their clinical consequences in the form of inborn errors in metabolism and neurodegenerative disorders, among others. Some of them are accompanied by skin symptoms such as ichthyosis and ichthyosiform erythroderma. In the following review, the structure of the skin is briefly characterized and the most important lipid components of the skin are presented. The focus is also on providing an overview of selected proteins involved in the metabolism of VLCFAs and ULCFAs in the skin.

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Section: Introductionmentioning

confidence: 99%

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Zwara

Wertheim–Tysarowska²,

Mika

2021

Front. Med.

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“…Various pure and compound heterozygous mutations in the PNPLA1 gene have been identified from a registry of human ichthyosis patients. To date, approximately 59 pathogenic mutations in the PNPLA1 gene have been reported ( Table 1 ) [ 2 , 4 , 24 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. These mutations include 35 missense mutations, four code-shifting mutations, eight nonsense mutations, four deletion mutations, three splice-site mutations, two early termination mutations, and one full code mutation.…”

Section: Mutations Of Pnpla1 Cause Arcimentioning

confidence: 99%

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

et al. 2022

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The stratum corneum of the epidermis acts as a life-sustaining permeability barrier. Unique heterogeneous ceramides, especially ω-O-acylceramides, are key components for the formation of stable lamellar membrane structures in the stratum corneum and are essential for a vital epidermal permeability barrier. Several enzymes involved in acylceramide synthesis have been demonstrated to be associated with ichthyosis. The function of patatin-like phospholipase domain-containing protein 1 (PNPLA1) was a mystery until the finding that PNPLA1 gene mutations were involved in autosomal-recessive congenital ichthyosis (ARCI) patients, both humans and dogs. PNPLA1 plays an essential role in the biosynthesis of acylceramide as a CoA-independent transacylase. PNPLA1 gene mutations cause decreased acylceramide levels and impaired skin barrier function. More and more mutations in PNPLA1 genes have been identified in recent years. Herein, we describe the structural and functional specificity of PNPLA1, highlight its critical roles in acylceramide synthesis and skin barrier maintenance, and summarize the PNPLA1 mutations currently identified in ARCI patients.

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Highlights of Gene and Cell Therapy for Epidermolysis Bullosa and Ichthyosis

Koutsoukos,

Bilousova

2024

Dermatol Ther (Heidelb)

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Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis

Cited by 4 publications

References 22 publications

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

Highlights of Gene and Cell Therapy for Epidermolysis Bullosa and Ichthyosis

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