Rare Diseases Symptoms Automatic Extraction

Interactions between FATP4 and ichthyin in epidermal lipid processing may provide clues to the pathogenesis of autosomal recessive congenital ichthyosis.

[aniridia]

Autosomal recessive congenital ichthyosis (ARCI) is caused by mutations in 10 different genes, of which transglutaminase-1 (TGM1) predominates. A rare form is ichthyosis prematurity syndrome (IPS) caused by mutations in SLC27A4 encoding fatty acid transporter protein 4 (FATP4), believed to be an acyl-CoA synthetase activating long- and very-long-chain FA. Another ARCI is caused by mutations in NIPAL4, coding for ichthyin, which is proposed to be a magnesium transporter or a trans-membrane receptor. A possible interaction between FATP4 and ichthyin has not been studied before.To find common denominators in the pathogenesis of ARCI.FATP4 and ichthyin were analyzed by immunofluorescence and proximity ligation assay (PLA) in healthy and ARCI patient skin and in in vitro models of ARCI epidermis.Both proteins were expressed in the upper stratum granulosum of normal epidermis and PLA confirmed a close interaction between FATP4 and ichthyin. In IPS skin lacking FATP4 we found reduced ichthyin expression and this finding could be reproduced in organotypic epidermis with siRNA silenced SLC27A4. In contrast, increased FATP4 staining was found in patients with ichthyin (NIPAL4) mutations and in organotypic epidermis with silenced NIPAL4. In patients with TGM1 mutations, the expression of both FATP4 and ichthyin was increased, but the PLA signal was low probably indicating a malfunctioning protein interaction.Our study suggests that FATP4, ichthyin and TGM1 interact in lipid processing essential for maintaining the epidermal barrier function. It is also hypothesized that ichthyin serves as Mg(2+)-transporter for FATP4 in this process.

Diseases presenting "tgm1 mutations" symptom

  • aniridia
  • harlequin ichthyosis
  • lamellar ichthyosis

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