Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: The underlying genetic defects and pathomechanisms

Akiyama, Masashi

doi:10.1016/j.jdermsci.2006.01.003

Cited by 88 publications

(90 citation statements)

References 51 publications

(85 reference statements)

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“…In ichthyotic skin with ABCA12 deficiency, defective formation of the lipid layers is thought to result in a serious loss of barrier function and a likely extensive compensatory hyperkeratosis [Akiyama, 2006b].…”

Section: Biological Significance; Pathomechanisms Of Ichthyosis Involmentioning

confidence: 99%

ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

2010

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Mutations in ABCA12 have been described in autosomal recessive congenital ichthyoses (ARCI) including harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). HI shows the most severe phenotype. CIE and LI are clinically characterized by fine, whitish scales on a background of erythematous skin, and large, thick, dark scales over the entire body without serious background erythroderma, respectively. To date, a total of 56 ABCA12 mutations have been reported in 66 ARCI families including 48 HI, 10 LI, and 8 CIE families of African, European, Pakistani/Indian, and Japanese origin (online database: http://www.derm-hokudai.jp/ABCA12/). A total of 62.5% of reported ABCA12 mutations are expected to lead to truncated proteins. Most mutations in HI are truncation mutations and homozygous or compound heterozygous truncation mutations always results in HI phenotype. In CIE families, at least one mutation on each allele is typically a missense mutation. Combinations of missense mutations in the first ATPbinding cassette of ABCA12 underlie the LI phenotype. ABCA12 is a keratinocyte lipid transporter associated with lipid transport in lamellar granules, and loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in an ichthyotic phenotype. Recent work using mouse models confirmed ABCA12 roles in skin barrier formation.

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Section: Biological Significance; Pathomechanisms Of Ichthyosis Involmentioning

confidence: 99%

ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

2010

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“…The pathophysiology of ARCI revolves around deficiencies in intercellular lipid [6] . The lipid that forms the 'cement' between corneocytes, and forms the epidermal barrier, originates from lamellar granules which are located in the granular cell layer [7,8] .…”

Section: Introductionmentioning

confidence: 99%

“…Ichthyin-like proteins are localized on the plasma membrane, and share a homology to both transporters and G-protein-coupled receptors [2,6] . Ichthyin is thought to be a membrane receptor for the trioxilins A3 and B3, which are components of the hepoxilin pathway, but its function is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

NIPAL4/Ichthyin Is Expressed in the Granular Layer of Human Epidermis and Mutated in Two Pakistani Families with Autosomal Recessive Ichthyosis

et al. 2009

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Background: Autosomal recessive congenital ichthyosis (ARCI) can be divided into 3 types including lamellar ichthyosis (OMIM 242304), nonbullous congenital ichthyosiform erythroderma (OMIM 242100) and harlequin ichthyosis (OMIM 242500). The last type is uncommon since newborns with harlequin ichthyosis usually die shortly after birth. Several genes have been linked to ARCI, but these represent only 60% of the known genetic causes of this condition. Methods: After having performed a linkage analysis, we analyzed the DNA of 2 consanguineous Pakistani families with ARCI for NIPAL4 mutations and performed in situ hybridization (ISH) for NIPAL4 mRNA in the epidermis. Results: The haplotype analysis revealed a linkage to chromosome 5, and we identified a recurrent missense mutation, p.A176D, in affected individuals from both families. We also determined by ISH that NIPAL4 mRNA is highly expressed in the granular cell layer of the epidermis, consistent with the ARCI phenotype. Conclusion: Our results expand the spectrum of the clinical manifestations of the NIPAL4 gene and further extend our understanding of its molecular function.

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“…Se han relacionado las alteraciones en el ABCA12 con la alteración en la distribución y el transporte de glucosilceramidas y con la disminución de los niveles de hidroxiceramidas, uno de los componentes principales de la barrera lipídica, a nivel del espacio intercelular 3,6,92,93 . La enorme hiperqueratosis que se produce en estos pacientes podría ser una respuesta compensadora ante el defecto de la barrera lipídica 94 , o deberse a la falta de descamación de los corneocitos 93 . Los defectos en el transporte de ciertas proteasas, como la calicreína 5 y la catepsina D, causadas por las alteraciones en los cuerpos lamelares, podrían determinar la deficiente descamación 95 .…”

Section: Abca12unclassified

Ictiosis congénitas autosómicas recesivas

Rodríguez-Pazos

Ginarte

Vega

et al. 2013

Actas Dermo-Sifiliográficas

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Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: The underlying genetic defects and pathomechanisms

Cited by 88 publications

References 51 publications

ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

<i>NIPAL4/Ichthyin</i> Is Expressed in the Granular Layer of Human Epidermis and Mutated in Two Pakistani Families with Autosomal Recessive Ichthyosis

Ictiosis congénitas autosómicas recesivas

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