Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis from Norway
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Lamellar ichthyosis
Steroid sulfatase
Tissue transglutaminase
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Background: Lamellar ichthyosis is an autosomal recessive type of rare skin disorders characterized with defective epidermis leading hyperkeratosis with brownish-gray scales over the body. These patients are born as collodion babies and may also exhibit additional features like erythema, ectropion, and eclabium. This disease is mainly caused by homozygous and compound heterozygous alterations in transglutaminase 1 encoding gene (TGM1), which is located on 14q12. Case presentation: This study reports the genetic analysis of a 4-year Saudi girl presenting lamellar ichthyosis. She was the first child of unrelated parents. The family had no previous history of the disease phenotype. She was born as a collodion baby without any prenatal complications. At the time of this study she had developed rough scaly skin on her legs, arms and trunk regions with thick palms and soles. Whole exome sequencing (WES) followed by Sanger sequence validation identified a novel compound heterozygous variant in TGM1 gene. The paternal variant was a missense transition (c.1141G>A; p.Ala381Thr) present at exon 7, while maternal variant (c.758-1G>C) was present at the intron4-exon5 boundary. To the best of our knowledge these variants had not been reported before in TGM1 gene. Conclusion: In isolated and inbred populations, homozygous variants are identified more frequently; however, our results suggest that compound heterozygous variants should also be considered especially when the marriages are not consanguineous.
Lamellar ichthyosis
Compound heterozygosity
Congenital ichthyosis
Collodion
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Lamellar ichthyosis (nonbullous congenital ichthyosis) has been explained as an autosomal recessive trait. We have found an autosomal dominant type of this disorder. Four patients, belonging to three consecutive generations of a family, were affected from birth. The disorder was characterized by large, dark brown scales covering the entire body including flexural folds, palms and soles. X‐linked recessive ichthyosis was excluded by clinical appearance, pattern of transmission and normal electrophoretic mobility of beta‐lipoproteins. Autosomal dominant ichthyosis vulgaris and bullous ichthyosiform erythroderma were excluded by the histological and ultrastructural features. In the absence of a positive family history, this skin disorder would have been taken for autosomal recessive lamellar ichthyosis. This new autosomal dominant type of ichthyosis should be considered for differential diagnosis, when genetic counselling is given in a sporadic case of lamellar ichthyosis.
Lamellar ichthyosis
Congenital ichthyosis
Dyskeratosis
Ichthyosis vulgaris
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Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive lamellar ichthyosis due to transglutaminase-1 (TGase-1) gene mutations leading to a temperature sensitive phenotype. It is characterized by dark-grey or brownish scaling restricted to the 'bathing suit' areas, whereas the extremities and central face are almost completely spared. We report a 2-year-old African girl with BSI with ultrastructural and biochemical demonstration of TGase-1 deficiency over the affected skin. TGase-1 gene analysis disclosed the homozygous p.R315L mutation, which may lead to a temperature sensitive dysfunction of the enzyme.
Lamellar ichthyosis
Bathing
Congenital ichthyosis
Tissue transglutaminase
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The transglutaminase 1 (TGM1) gene is a major causative gene of autosomal recessive congenital ichthyoses (ARCI), including lamellar ichthyosis (LI), congenital ichthyosiform erythroderma, self-healing/self-improving collodion baby, and bathing suit ichthyosis (BSI) [1, 2]. Additionally, a mutation in the epidermal lipase N gene (LIPN) was found to cause a late-onset form of ARCI [3]. To date, 12 genes responsible for ARCI have been identified: TGM1, ALOX12B, ALOXE3, ABCA12, CYP4F22, NIPAL4, SDR9C7, [...]
Lamellar ichthyosis
Congenital ichthyosis
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Lamellar ichthyosis
Congenital ichthyosis
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Lamellar ichthyosis
Tissue transglutaminase
Steroid sulfatase
Genetic linkage
Congenital ichthyosis
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Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification.ARCI is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis.Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1, are one of the causes of ARCI.The transglutaminase 1enzyme, is critical for the assembly of the cornified cell envelope in terminally differentiating keratinocytes.In this study a nine-year old boy who presented with ARCI.The whole exome sequencing WES of transglutaminase-1 gene was investigated.The patient harbored a homozygeous mutation of C.1165T>C transition located in exon8 of TGM1 gene, resulting in the substitution of argenine by serine at amino acid position 389.The parents and one of the sibs were hetrozygeous for the variant and one was homozygeous for wild allele.The mutated allele was not found in controls.This mutation localized in this study correspond to the core catalytic core domain of enzyme, based on provean algorithm, the variant at position level was predicted to decrease TGM1 Enzyme activity by producing an unstable protein.
Congenital ichthyosis
Tissue transglutaminase
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Congenital ichthyosis
Tissue transglutaminase
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Linked Article: Zimmer et al. Br J Dermatol 2017; 177:445–455.
Congenital ichthyosis
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Lamellar ichthyosis
Tissue transglutaminase
Identification
Congenital ichthyosis
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