Filaggrin mutations are associated with ichthyosis vulgaris in the Southern Chinese population

Filaggrin (FLG) plays an important role in the epidermal barrier function, which identified in patients with ichthyosis vulgaris(IV).To study the genetics of FLG mutations in Southern Chinese patients with IV. We evaluated the influence of five mutations (3321 delA, 441delA, 1249 insG, E1795X and S3296X) in a cohort of 65 IV Chinese patients and in 100 control individuals using the Sequenom? MassARRAY? system. The null allele frequency of 3321delA was 52.31%(34/65). FLG mutation 441delA was only found in one IV patients. FLG mutations 1249insG, E1795X and S3296X were not found in these patients. These findings show that the mutation 3321delA represent the most frequent genetic cause in Southern Chinese IV patients. Our findings confirm and extend the knowledge of the influence of FLG mutations in IV.

Novel Pathogenic Mutation of PNPLA1 Identified in Autosomal Recessive Congenital Ichthyosis:A Case Report

Autosomal recessive congenital ichthyosis(ARCI)is characterized by being born as collodion babies,hyperkeratosis,and skin scaling.We described a collodion baby at birth with mild ectropion,eclabium,and syndactyly.Whole exome sequencing showed a compound heterozygous variant c.[56C>A],p.(Ser19X)and c.[100G>A],p.(Ala34Thr)in the PNPLA1 gene[NM_001145717;exon 1].The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride toω-hydroxy fatty acid in ceramide,thus giving rise toω-O-acylceramide,a particular class of sphingolipids that is essential for skin barrier function.The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein.This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.

X linked recessive ichthyosis: Current concepts

In the present review, we describe the most importantaspects of the X-linked ichthyosis(XLI) and make a compilation of the some historic details of the disease. The aim of the present study is an update of the XLI. Historical, clinical, epidemiological, and molecular aspects are described through the text. Recessive XLI is a relatively common genodermatosis affecting different ethnic groups. With a high spectrum of the clinical manifestations due to environmental factors, the disease has a genetic heterogeneity that goes from a point mutation to a large deletion involving several genes to produce a contiguous gene syndrome. Most XLI patients harbor complete STS gene deletion and flanked sequences; seven intragenic deletions and 14 point mutations with a complete loss of the steroid sulfatase activity have been reported worldwide. In this study, we review current knowledge about the disease.

A Multiplex PCR-Based Next-Generation Sequencing Approach Has Detected a Common Large Deletion in STS Gene in a Patient with X-Linked Ichthyosis

Several nuclear genes have been found to be linked to ichthyosis, and Next Generation Sequencing approach on panels of targeted genes has turned out to be particularly useful in analyzing diseases characterized by significant genetic and phenotypic heterogeneity. We developed a panel of 26 genes to be screened with the Ion Personal Genome Machine (PGM) for causative mutations relating to ichthyosis. Sequencing runs were obtained from a patient with ichthyosis using the Ion Torrent PGM and then processed with Ion Torrent Suite, Variant Caller, Coverage Analysis and wANNOVER tools. No causative mutations were found using Variant Caller and wANNOVER softwares, whereas the “Coverage Analysis” tool revealed a common large deletion in STS gene in a patient with X-linked ichthyosis. Identification of indels in Next Generation Sequencing (NGS) data is a veritable challenge. This study demonstrates the efficacy and effectiveness of using NGS approach to detect large deletions without resorting to specific algorithms for “indel” detection. Our results indicate that the NGS panel is a useful, rapid and cost-effective screening test for patients whose features are suggestive of a genetic etiology involving one of the genes embedded in the panel. It is an excellent alternative to Sanger sequencing as for costs, ease of analysis, and turnaround time.

Clinical and genetic findings in 13 Chinese children with keratinopathic ichthyosis

Importance:Keratinopathic ichthyosis(KPI)represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1,KRT2,or KRT10 genes.In KPI,the relationship between genotype and phenotype is complex.Objective:To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.Methods:Clinical data were collected from 13 children diagnosed with KPI,and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel,and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.Results:Genetic analysis identified missense mutations in either KRT1 or KRT10 in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis.A missense hotspot mutation in KRT2 was identified in one patient with superficial epidermolytic ichthyosis.Additionally,two truncation mutations in KRT10 were detected,leading to the development of generalized ichthyosiform erythroderma.Ear malformation and ectropion at birth,scalp involvement,and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.Interpretation:We analyzed the genotype-phenotype correlations in KPI,revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics.Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.

Homozygous Nonsense Mutation in SDR9C7 in a Chinese Patient With Autosomal Recessive Congenital Ichthyosis

Introduction:Autosomal recessive congenital ichthyosis(ARCI)is a heterogeneous group of cornification disorders.To date,14 genes have been found to be related to ARCI.Case presentation:A 23-year-old woman developed generalized erythroderma and scales over her trunk and limbs shortly after birth,followed by recurrent blisters and nail deformities.A diagnosis of ARCI was made based on her clinical manifestations,family history,and genetic analysis,which revealed a homozygous mutation inSDR9C7(c.187C>T,p.Q63X).Discussion:Most genes responsible for ARCI are associated with epidermal lipid metabolism,which contributes to the cutaneous barrier.SDR9C7,which encodes short-chain dehydrogenase/reductase family 9C member 7,has also been recently found to play vital roles in this process by regulating ceramide binding to the epidermal cornified cell envelope.For patients clinically suspected to have ARCI,recurrent onychomycosis is a strong indication that they carry aSDR9C7 gene mutation.Conclusion:Remarkable phenotypic and genotypic heterogeneity exists among patients with ARCI.Genetic analysis is an effective tool in diagnosing this and other hereditary diseases.Our patient developed recurrent onychomycosis,a typical presentation of ARCI caused bySDR9C7 mutation,and the unusual blisters further expand the clinical phenotypic spectrum of ARCI.

A harlequin ichthyosis pig model with a novel ABCA12 mutation can be rescued by acitretin treatment

Harlequin ichthyosis (HI) is a severe genetic skin disorder and caused by mutation in the ATP-binding cassette A12 (ABCA12) gene. The retinoid administration has dramatically improved long-term survival of HI, but improvements are still needed. However, the ABCA12 null mice failed to respond to retinoid treatment, which impedes the development of novel cure strategies for HI. Here we generated an ethylnitrosourea mutagenic HI pig model (named Z9), which carries a novel deep intronic mutation IVS49-727 A>G in the ABCA12 gene, resulting in abnormal mRNA splicing and truncated protein production. Z9 pigs exhibit significant clinical symptom as human patients with HI. Most importantly, systemic retinoid treatment significantly prolonged the life span of the mutant pigs via improving epidermal maturation, decreasing epidermal apoptosis, and triggering the expression of ABCA6. Taken together, this pig model perfectly resembles the clinical symptom and molecular pathology of patients with HI and will be useful for understanding mechanistic insight and developing therapeutic strategies.

Prenatal Diagnosis of Harlequin Ichthyosis:A Case Report

Harlequin ichthyosis is a severe autosomal recessive skin disorder.Most deaths occur within the first few days after birth,and the survivors still have severe chronic skin disease throughout their lives.Almost all cases were associated with a pathogenic variant of adenosine triphosphate binding cassette transporter,subfamily A,member 12(ABCA12)gene.We described a case of HI diagnosed by ultrasound examination during the second-trimester and genetic diagnosis reveal two novel heterozygous ABCA12 mutations c.2563-2570delinsGGCAATT,p.(Leu855Glyfs*13),and c.6116delT,p.(Met2039Argfs*8)by the next-generation DNA sequencing,which further enriched our understanding of the pathogenic variation of ABCA12 gene.

Use of two combination creams for the treatment of ichthyoses and ichthyosiform disorders

Treatment options for ichthyosis and ichthyosiform disorders are limited and often unsatisfactory.Twenty-four patients used combination creams of 2%cholesterol with 2%lovastatin,and 10%glycolic acid with 0.025% tretinoin and 2%ketoconazole daily.At one month(n=20),the average percent reduction in severity scores was 40%,and at three months(n=10),it was 60.3%.Side effects were mainly mild irritation.These findings suggest that these two combination creams could be beneficial in the treatment of ichthyosiform disorders.

A Case of Complete Neu-Laxova Syndrome: Report and Literature Review

Neu-Laxova syndrome (NLS) is a rare autosomal recessive and early fatal disease. It is a complex entity that includes intrauterine growth retardation, abnormal facial structure, limb and skeletal abnormalities, and ichthyosis and severe malformations of the central nervous system. We report a rare case of recurrence of Neu-Laxova syndrome in a 32-year-old pauciparous woman, which occurred after a first cousin’s consanguineous marriage. Typical ultrasound findings included hydramnios, severe intrauterine growth restriction, craniofacial and central nervous system abnormalities such as ventriculomegaly. The newborn shows a terrible face with a usual craniofacial aspect, eyeball proptosis, puffy hands and feet, large bilateral cleft lip/palate, severe hall body ichthyosis. The overcome was fatal, the death occurred in less than one hour after birth. Consanguinity remains the most implicated cause which is high in developing countries. Prenatal serial ultrasound examinations with genetic counselling should be performed on high-risk pregnant women to terminate affected pregnancies.