Vahlquist A, Bygum A, Gånemo A et al.Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients. J Invest Dermatol 130:438-443

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Journal of Investigative Dermatology (Impact Factor: 7.22). 11/2009; 130(2):438-43. DOI: 10.1038/jid.2009.346
Source: PubMed


Infants born with autosomal recessive congenital ichthyosis (ARCI) are often encapsulated in a collodion membrane, which shows a lamellar or erythrodermic type of ichthyosis upon shedding. However, some babies show a nearly normal underlying skin after several weeks, a phenotype called "self-healing collodion baby" (SHCB). Mutations in two genes, TGM1 and ALOX12B, have previously been implicated in the etiology of SHCB, but the full genotypic spectrum remains to be determined. DNA sequencing in 11 Swedish and 4 Danish SHCB patients showed ALOX12B mutations in eight cases, ALOXE3 mutations in three cases, and TGM1 mutations in one case. In three patients, we could not find mutations in any of the known ARCI genes. In all cases, a spontaneous shedding of the collodion membrane occurred 2-4 weeks after birth. When re-examined at 2-37 years of age, the patients showed skin xerosis, a mild or focal scaling, palmar hyperlinearity with keratoderma, and a frequent appearance of red cheeks and anhidrosis. Thus, we propose replacing SHCB with the term "self-improving collodion ichthyosis" (SICI). In conclusion, ALOX12B mutations are the leading cause of SICI in Scandinavia, followed by ALOXE3 mutations, which have not been previously associated with this variant of ARCI.

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Available from: Judith Fischer, Jul 15, 2014
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    • "In humans autosomal recessive congenital ichthyosis (ARCI) is a group of skin diseases, which is characterized by intense scaling [93]. Naturally occurring mutations in the ALOX12B and ALOXE3 genes have frequently been detected in ichthyosis patients [94] [95]. In a large group of 250 ARCI patients [96] 11 previously unidentified mutations have been described in the two LOX genes in 21 ARCI patients from 19 unrelated families. "
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    ABSTRACT: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin barrier diseases due inter alia to mutations in transglutaminase-1 (TGM1), in lipoxygenases (LOXs) of the hepoxilin pathway, and in ichthyin, a putative Mg(2+) transporter encoded by the NIPAL4 gene. In search of a common pathogenic pathway for ARCI, we investigated the epidermal expression of TGM1, 12R-LOX, eLOX-3, and ichthyin in skin biopsies from four healthy controls and nine patients with ARCI. In healthy skin, TGM1, ichthyin, and the LOX enzymes were predominantly expressed in the upper epidermis where colocalization signals could also be demonstrated by in situ proximity ligation assay. In patients with ALOX12B mutations and abnormal 12R-LOX expression, the colocalization signal for eLOX-3 and TGM1 was increased 4-fold. In contrast, patients with NIPAL4 mutations and abnormal ichthyin expression showed increased 12R-LOX and eLOX-3 staining and a colocalization signal of these LOXs that was three times the normal intensity. Treatment of these patients with a retinoid-mimetic drug, liarozole, normalized the expression of 12R-LOX and attenuated the colocalization signal. Altogether, our data indicate that ichthyin and TGM1 are functionally closely related in the lipid processing and that this metabolic pathway can be modified by retinoids.
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