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Masashi Akiyama - One of the best experts on this subject based on the ideXlab platform.
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Novel TGM1 missense mutation p.Arg727Gln in a case of self-healing collodion baby.
Acta Dermato-venereologica, 2020Co-Authors: Kana Tanahashi, Kazumitsu Sugiura, Kenji Asagoe, Yumi Aoyama, Keiji Iwatsuki, Masashi AkiyamaAbstract:Collodion babies are newborns encased in a glistening membrane that cracks in a characteristic manner within 48 h and desquamates in large lamellae after a few days. Most collodion babies later develop one of the several types of autosomal recessive congenital ichthyoses (ARCI), such as lamellar Ichthyosis (LI) or congenital ichthyosiform erythroderma; however, about 10% heal spontaneously (1). This healing condition is known as “self-healing collodion baby” or “self-improving collodion baby” (SHCB/SICB). Raghunath et al. (1) showed that this phenotype is possibly a hydrostatic pressuresensitive phenotype of TGM1 mutations. The SHCB/ SICB phenotype was subsequently reported in patients with ALOX12B and ALOXE3 mutations (2). To date, few reports on SHCB/SICB cases with TGM1 mutations have been published (1–4). TGM1 is the most commonly involved gene in ARCI, and encodes transglutaminase-1 (TGase-1) (1, 5–8). Here, we describe an ARCI patient with a novel TGM1 mutation who presented at birth with a collodion membrane but spontaneously healed within 2 months without any skin manifestations.
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corneocyte lipid envelope cle the key structure for skin barrier function and Ichthyosis pathogenesis
Journal of Dermatological Science, 2017Co-Authors: Masashi AkiyamaAbstract:Abstract Research on the genetic abnormalities and pathogenetic processes of ichthyoses has progressed remarkably, and many causative genes and molecules have been identified in ichthyoses and Ichthyosis syndromes. Most of the genes/molecules causative of Ichthyosis are associated with the barrier function of the stratum corneum, and defects in the skin barrier play important roles in the pathogenesis of various Ichthyosis phenotypes. It has been elucidated that, of the Ichthyosis-causative genes, ABCA12, ALOXE3, ALOX12B, CYP4F22, CERS3, ABHD5, PNPLA1 and ELOVL4 work in the formation of the corneocyte lipid envelope (CLE), a structure that is essential to sound skin barrier function. The CLE mostly consists of ultra-long-chain (ULC) ceramides derived from ULC-acylceramide (EOS; a combination of esterified ω-hydroxy fatty acids and sphingosines). In this review, I shed light on the synthesis, metabolism and transport of epidermal ceramides, especially on ULC-acylceramide and the processes of CLE formation. In addition, I summarize the pathogeneses of various ichthyoses and Ichthyosis syndromes from the aspects of abnormal synthesis of ULC-acylceramide and malformation of the CLE. Investigations on the pathomechanisms of ichthyoses have provided novel knowledge on the synthesis and metabolism of ceramides in the epidermis. Conversely, research on the dynamics of epidermal ceramides has contributed to the elucidation of the pathogenesis of ichthyoses. Advances in our understanding of the biology of epidermal lipids and the disease pathogeneses of ichthyoses and Ichthyosis syndromes promise to provide clues for the development of effective therapies for Ichthyosis patients in the near future.
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Inherited Ichthyosis: Non‐syndromic forms
Journal of Dermatology, 2016Co-Authors: Takuya Takeichi, Masashi AkiyamaAbstract:Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non-syndromic ichthyoses and Ichthyosis syndromes. Non-syndromic ichthyoses are characterized by the phenotypic expression of the disorder being seen only in the skin. Non-syndromic ichthyoses include Ichthyosis vulgaris, recessive X-linked Ichthyosis, autosomal recessive congenital Ichthyosis, keratinopathic Ichthyosis and other forms. This review focuses on updates for each type of non-syndromic Ichthyosis, highlighting molecular mechanisms and phenotype/genotype correlations. Included in autosomal recessive congenital Ichthyosis are three of the major phenotypes (harlequin Ichthyosis, lamellar Ichthyosis and congenital ichthyosiform erythroderma) and three of the minor subtypes (self-healing collodion baby, acral self-healing collodion baby and bathing suit Ichthyosis). Keratinopathic Ichthyosis is proposed as an umbrella term for ichthyoses caused by mutations in keratin genes. Next-generation sequencing technologies have become powerful tools for the diagnosis of inherited ichthyoses and the discovery of their genetic causes. This article reviews the current understanding of molecular pathomechanisms for non-syndromic ichthyoses and explores future perspectives.
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inherited Ichthyosis non syndromic forms
Journal of Dermatology, 2016Co-Authors: Takuya Takeichi, Masashi AkiyamaAbstract:Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non-syndromic ichthyoses and Ichthyosis syndromes. Non-syndromic ichthyoses are characterized by the phenotypic expression of the disorder being seen only in the skin. Non-syndromic ichthyoses include Ichthyosis vulgaris, recessive X-linked Ichthyosis, autosomal recessive congenital Ichthyosis, keratinopathic Ichthyosis and other forms. This review focuses on updates for each type of non-syndromic Ichthyosis, highlighting molecular mechanisms and phenotype/genotype correlations. Included in autosomal recessive congenital Ichthyosis are three of the major phenotypes (harlequin Ichthyosis, lamellar Ichthyosis and congenital ichthyosiform erythroderma) and three of the minor subtypes (self-healing collodion baby, acral self-healing collodion baby and bathing suit Ichthyosis). Keratinopathic Ichthyosis is proposed as an umbrella term for ichthyoses caused by mutations in keratin genes. Next-generation sequencing technologies have become powerful tools for the diagnosis of inherited ichthyoses and the discovery of their genetic causes. This article reviews the current understanding of molecular pathomechanisms for non-syndromic ichthyoses and explores future perspectives.
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malignant skin tumours in patients with inherited Ichthyosis
British Journal of Dermatology, 2011Co-Authors: Ken Natsuga, Masashi Akiyama, Hiroshi ShimizuAbstract:Summary Inherited ichthyoses are rare genodermatoses caused by mutations in the genes involved in epidermal development. Although there have been case reports on patients with Ichthyosis who developed skin malignancies, it is still unknown whether or not patients with Ichthyosis have an increased risk of skin malignancies. Here, we review case series of skin malignancies in patients with Ichthyosis and show biological findings which might lead to cancer susceptibility. A survey of the literature revealed 28 cases of inherited ichthyoses with skin malignancy, including 12 cases of keratitis–Ichthyosis–deafness (KID) syndrome, seven of autosomal recessive congenital Ichthyosis, three of Netherton syndrome and six of miscellaneous Ichthyosis. Twenty-four of the 28 cases developed single or multiple squamous cell carcinomas (SCCs). The age at diagnosis of the first skin malignancy ranged from 15 to 54 years. As patients with these particular subtypes of Ichthyosis seem to be prone to skin malignancies, including SCC, at an unusually young age, routine cancer surveillance of these patients is strongly recommended.
K. -m. Niemi - One of the best experts on this subject based on the ideXlab platform.
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Clinical, light and electron microscopic features of recessive Ichthyosis congenita type III
Archives of Dermatological Research, 1992Co-Authors: K. -m. Niemi, L. Kanerva, C. -f. Wahlgren, J. IgnatiusAbstract:The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital Ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the Ichthyosis was variable, in contrast to other patients described under the heading recessive congenital Ichthyosis.
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Recessive Ichthyosis congenita type II
Archives of Dermatological Research, 1991Co-Authors: K. -m. Niemi, L. Kanerva, K. KuokkanenAbstract:In the hetereogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale Ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe Ichthyosis, but good general health and no associated symptoms. This disorder has recently been named ‘Ichthyosis congenita type II’ by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis ‘lamellar Ichthyosis’.
L. Kanerva - One of the best experts on this subject based on the ideXlab platform.
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Clinical, light and electron microscopic features of recessive Ichthyosis congenita type III
Archives of Dermatological Research, 1992Co-Authors: K. -m. Niemi, L. Kanerva, C. -f. Wahlgren, J. IgnatiusAbstract:The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital Ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the Ichthyosis was variable, in contrast to other patients described under the heading recessive congenital Ichthyosis.
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Recessive Ichthyosis congenita type II
Archives of Dermatological Research, 1991Co-Authors: K. -m. Niemi, L. Kanerva, K. KuokkanenAbstract:In the hetereogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale Ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe Ichthyosis, but good general health and no associated symptoms. This disorder has recently been named ‘Ichthyosis congenita type II’ by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis ‘lamellar Ichthyosis’.
Hassan Vahidnezhad - One of the best experts on this subject based on the ideXlab platform.
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autosomal recessive congenital Ichthyosis cers3 mutations identified by a next generation sequencing panel targeting Ichthyosis genes
European Journal of Human Genetics, 2017Co-Authors: Leila Youssefian, Hassan Vahidnezhad, Amir Hossein Saeidian, Soheila Sotoudeh, Hamidreza Mahmoudi, Maryam Daneshpazhooh, Nessa Aghazadeh, Rebecca J Adams, Alireza GhanadanAbstract:There are at least 38 mutant genes known to be associated with the Ichthyosis phenotypes, and autosomal recessive congenital Ichthyosis (ARCI) is a specific subgroup caused by mutations in 13 different genes. Mutations in some of these genes, such as CERS3 with only two previous reports, are rare. In this study, we identified mutations in candidate genes in consanguineous families with ARCI with a next generation sequencing (NGS) array that incorporates 38 Ichthyosis associated genes. We applied this sequencing array to DNA from 140 Ichthyosis families with high prevalence of consanguinity. Among these patients we identified six distinct, previously unreported mutations in CERS3 in six Iranian families. These mutations in each family co-segregated with the Ichthyosis phenotype. The patients demonstrated collodion membrane at birth, acrogeria, generalized scaling, and hyperlinearity of the palms and soles. The presence of a significant percentage of CERS3 mutations in our cohort depicts a marked difference between the etiology of ichthyoses in genetically poorly characterized regions and well-characterized western populations. Also, it shows that rare alleles are more prevalent in the gene pool of consanguineous populations and emphasizes the importance of these population studies for better understanding of Ichthyosis pathogenesis.
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expanding the genotypic spectrum of bathing suit Ichthyosis
JAMA Dermatology, 2017Co-Authors: Nareh V Marukian, Brittany G. Craiglow, Rong Hua Hu, Leonard M Milstone, Jing Zhou, Amy Theos, Hande Kaymakcalan, Deniz A Akkaya, Jouni Uitto, Hassan VahidnezhadAbstract:Importance Bathing suit Ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit Ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene ( TGM1 ). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital Ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. Objective To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. Design, Setting, and Participants A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1 . Main Outcomes and Measures Phenotypic and genotypic characteristics in these patients from birth onward. Results Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non–temperature-sensitive forms of congenital Ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. Conclusions and Relevance Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.
J. Ignatius - One of the best experts on this subject based on the ideXlab platform.
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Clinical, light and electron microscopic features of recessive Ichthyosis congenita type III
Archives of Dermatological Research, 1992Co-Authors: K. -m. Niemi, L. Kanerva, C. -f. Wahlgren, J. IgnatiusAbstract:The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital Ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the Ichthyosis was variable, in contrast to other patients described under the heading recessive congenital Ichthyosis.