Autosomal Recessive Congenital Ichthyosis Research Articles

Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in CLDN1.

Autosomal recessive congenital ichthyosis (ARCI) refers to a large and genetically heterogenous group of non-syndromic disorders of cornification featuring diffuse scaling. Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome is a rare autosomal recessive syndromic form of ichthyosis. The disease usually results from premature termination codon-causing pathogenic variants in CLDN1 encoding CLAUDIN-1 (CLDN1). We used whole exome sequencing (WES), Sanger sequencing, 3D protein modeling, Western blotting, and immunofluorescence confocal microscopy to delineate the genetic basis of ichthyosis in two siblings with ichthyosis but no other ectodermal abnormalities. One of the two siblings underwent liver transplantation in early childhood due to biliary atresia. Both patients were found to carry a homozygous missense pathogenic variant, c.242G>A (p.Arg81His), in CLDN1. The variant resulted in decreased CLDN1 expression in patient skin. 3D protein modeling predicted that p.Arg81His induces deleterious conformational changes. Accordingly, HaCaT cells transfected with a construct expressing the mutant CLDN1 cDNA featured decreased levels and mislocation of CLDN1 as compared with cells expressing the wildtype cDNA. In conclusion, we describe the first pathogenic missense variant in CLDN1 shown to result in ARCI.

Impaired production of skin barrier lipid acylceramides and abnormal localization of PNPLA1 due to ichthyosis-causing mutations in PNPLA1

BackgroundPNPLA1 is a causative gene of autosomal recessive congenital ichthyosis. The transacylase PNPLA1 produces ω-O-acylceramides (acylceramides), lipids essential for the skin barrier function, by catalyzing the transfer of a linoleic acid from triglycerides to ω-hydroxyceramides. ObjectiveWe aimed to validate the involvement of PNPLA1 mutations found in ichthyosis patients in the pathogenesis and elucidate the correlation between the effects of these mutations on acylceramide-producing activity and ichthyosis pathology. MethodsAcylceramide-producing activity of PNPLA1 mutants was investigated using a cell-based assay system, in which wild-type PNPLA1 or each PNPLA1 mutant was co-overexpressed with the enzymes involved in acylceramide synthesis. The effect of each mutation on the ABHD5-dependent lipid droplet localization of PNPLA1 was examined through indirect immunofluorescence microscopy. ResultsOf 16 PNPLA1 missense mutations, 15 mutations, except the C216R mutation, resulted in a complete loss of acylceramide-producing activity, while the C216R mutation weakly affected this activity. Intracellular localization of mutants with no activity varied among mutants. Two mutants (S19L and D172N) localized in lipid droplets, and eight mutants (S53L, S53W, A59V, T125N, D129E, R166C, P234S, and P235L) partially localized there. Five mutants (A34P, A34T, S53P, K141E, and P163L) localized throughout the cytosol. ConclusionThe PNPLA1 missense mutations examined in this study are responsible for ichthyosis pathology. The weak effect of C216R mutation on acylceramide-producing activity correlates with the mild symptoms of the ichthyosis patient. Sixteen PNPLA1 mutants were classified into four groups based on their acylceramide-producing activity and localization.

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis.

The stratum corneum of the epidermis acts as a life-sustaining permeability barrier. Unique heterogeneous ceramides, especially ω-O-acylceramides, are key components for the formation of stable lamellar membrane structures in the stratum corneum and are essential for a vital epidermal permeability barrier. Several enzymes involved in acylceramide synthesis have been demonstrated to be associated with ichthyosis. The function of patatin-like phospholipase domain-containing protein 1 (PNPLA1) was a mystery until the finding that PNPLA1 gene mutations were involved in autosomal-recessive congenital ichthyosis (ARCI) patients, both humans and dogs. PNPLA1 plays an essential role in the biosynthesis of acylceramide as a CoA-independent transacylase. PNPLA1 gene mutations cause decreased acylceramide levels and impaired skin barrier function. More and more mutations in PNPLA1 genes have been identified in recent years. Herein, we describe the structural and functional specificity of PNPLA1, highlight its critical roles in acylceramide synthesis and skin barrier maintenance, and summarize the PNPLA1 mutations currently identified in ARCI patients.

The CONTROL study: A randomized, double-blind vehicle-controlled phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis

The CONTROL study: A randomized, double-blind vehicle-controlled phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis

714 An essential role for CRL complex signaling in epidermal differentiation

Maintenance of skin homeostasis requires meticulous regulation of the induction, repression and degradation of key signaling factors governing progenitor cell homeostasis and terminal differentiation programs. Deregulation of these pathways is a hallmark of the skin barrier disruption often manifested in skin disease. Timed and controlled orchestration of these networks involves ubiquitin and ubiquitin-like proteins, as abnormal targeted degradation or post-translational modifications are evidenced in conditions harboring mutations in these pathways including xeroderma pigmentosum, autosomal recessive congenital ichthyosis, skin cancer, and dermatomyositis. By combining a CRISPR genetic screen of genes encoding ubiquitin and ubiquitin-like signaling proteins with single-cell RNA-sequencing of primary, differentiated keratinocytes, we demonstrate a cluster of 26 proteins with a marked impact on epidermal differentiation. Through analysis of individual gene targets, gene signatures and the cell state affected by these perturbations, we identify new functions for regulating differentiation and proliferation. We demonstrate specific receptor-adaptor-substrates tethered in Cullin-RING E3 ubiquitin ligase complexes (CRLs), having a dramatic effect on key differentiation pathways. This adaptor-receptor-substrate specific effect of CRLs determines terminal differentiation, which has implications for progenitor cell differentiation and therapeutic interventions of this pathway.

397 Characterization of ABCA12 gene variant by electron microscopy in an infant with an ichthyosiform dermatitis and MALT1 deficiency

The ABCA12 gene encodes an ATP-binding cassette transporter vital to skin barrier function. In keratinocytes, ABCA12 transports ceramides into the lumen of lamellar bodies as part of the widely conserved water barrier system. Alterations in the ABCA12 gene are associated with the autosomal recessive congenital ichthyoses: harlequin ichthyosis, non-bullous congenital ichthyosiform erythroderma, and lamellar ichthyosis. We report a 4-month-old female who presented with erythroderma, diffuse fine scale, and recurrent infections.

Genotype of autosomal recessive congenital ichthyosis from a tertiary care center in India.

Autosomal recessive congenital ichthyosis (ARCI) refers to non-syndromic ichthyosis caused by mutations in one of the 13 identified genes. There are limited data on the genotype of ARCI and its phenotypic correlation from India. The aim of this study was to characterize the genotype of ARCI among patients from the Indian subcontinent. Twenty-eight patients clinically diagnosed as ARCI were recruited prospectively from September 2017 to June 2019 (21months). DNA was extracted from peripheral blood and analyzed for the 13 described ARCI genes-TGM1, ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, and CASP14 by next-generation sequencing using an in-house panel. The variants identified were confirmed by Sanger sequencing and compared with known pathogenic variants to establish pathogenicity. We also attempted to correlate the phenotype with the genotype. Among the 28 patients recruited (M=17, F=11), we identified phenotypes of congenital ichthyosiform erythroderma in 12 (42.9%), 8 with lamellar ichthyosis (28.6%), 5 with intermediate phenotype (17.9%), and 3 with bathing suit ichthyosis (10.7%). Pathogenic and likely pathogenic variants were identified in 22 (78.6%) patients, involving 7 out of the 13 known ARCI genes while 6 (21.4%) did not have pathogenic variants. These included TGM1 mutation in 6 (21.4%), ALOX12B and ALOXE3 in 4 (14.3%) each, NIPAL4 and PNPLA1 in 3 (10.7%) each, and ABCA12 and CERS3 in 1 (3.6%) patient each. Previously unknown pathogenic variants were found in 59.1 % of patients. Our patients with ARCI were found to have genotypes as previously described in other populations.

Lessons on the value of long term follow-up from genetic counselling of a family with severe autosomal recessive congenital ichthyosis.

Lessons on the value of long term follow-up from genetic counselling of a family with severe autosomal recessive congenital ichthyosis.

Clinical and genetic analysis of a patient with autosomal recessive congenital ichthyosis due to compound heterozygous variants of ALOX12B gene

To explore the clinical and genetic characteristics of a pediatric patient suspected for Autosomal Recessive Congenital Ichthyosis (ARCI). Clinical data of the patient was analyzed. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Next-generation sequencing (NGS) was then carried out. Candidate variants were confirmed by Sanger sequencing. A variety of bioinformatic tools including Mutation Taster, PROVEAN, and PolyPhen2 were used to predict the pathogenicity of the variants based on guidelines from the American College of Medical Genetics and Genomics (ACMG). The patient, a 1-month-and-7-day-old male, had presented with cutaneous erythema and fine scaling of the whole body. NGS revealed that he has harbored compound heterozygous variants c.1579G>A (p.Val527Met) (paternal) and c.923T>C (p.Leu308Pro) (maternal) of the ALOX12B gene. The former was known to be likely pathogenic, while the latter was unreported previously and categorized as "likely pathogenic" based on the ACMG guidelines. Based on the clinical and genetic findings, the patient was diagnosed with ARCI. The c.1579G>A and c.923T>C variants of the ALOX12B genes probably underlay the ARCI in this patient. Above finding has enriched the spectrum of ALOX12B mutations and enabled molecular diagnosis of the patient, based on which genetic counseling and prenatal diagnosis may be provided.

Abstract 60: Rickets in congenital bullous ichthyosiform erythroderma

Introduction: Congenital ichthyosiform erythroderma (CIE), also known as bullous congenitalichthyosiform erythroderma is a rare type of the ichthyosis family of skin diseases which occurs in 1 in 200,000 to 300,000 births. CIE comes under the umbrella term autosomal recessive congenital ichthyosis (ARCI), which include non-syndromic congenital ichthyosis such as harlequinichthyosis and lamellar ichthyosis. Ichthyosiform erythroderma due to keratinizing disordersmaysuppress cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets.Description: A 8 year 10 months old female child presented with poor height gain from 5 years and inward bending of knees from 5 years. h/o hyperpigmented hyperkeratotic scaly dry skinfrombirth. She was diagnosed with Bullous ichythosiform erythroderma and was prescribed emollients by a dermatologist. She is born out of non-consangienous marriage, second in birth order has an elder and youngersibling who are apparently normal. Ichythyosis present from birth more during winter season. h/o delayed dentition present. No h/o constipation or weight gain. h/o delayed motor milestones present. Language and social skills normal. o/e height is 78 cms @ < -10.8 SDS; height age <2 years weight 10 kg @ < - 6 SDS ; weight age < 2 years inward bending of knees + ; forward bending of tibia + ; ichthyosis over lower limbs, abdomen and upper limb. Her labs showed low Vit D levels of 8.7 ng/ml; calcium of 7.5 mg/dl (8- 10 mg/dl); phosphorus 2.6 mg/ml (2.5-4.8 mg/dl); elevated serum Alkaline phosphatase of 1450 IU/L; serum PTH of 181 pg/ml; normal thyroid and renal profile. She was started on oral vitamin D3 supplements and calcium supplements.Discussion: Ichthyosiform erythroderma is of two types, one inherited as an autosomal dominant and the other as an autosomal recessive trait. The recessive form is nonbullous and is associated with growth retardation, oligophrenia, spastic paralysis, genital hypoplasia, hypotrichia and shortened life expectancy. In the autosomal dominant or bullous form, however, life expectancy is not shortened, and the associated symptoms include only seborrhoea of the head an probably polydipsia. Both types begin at birth and are localized mostly on the flexor surfaces. Nonbullous congenital ichthyosiform erythroderma is characterized by prominent erythroderma and fine white, superficial semiadherent scales. The majority of affected individuals are present at birth as collodion babies. Skin histology shows hyperkeratosis, an increase in stratum corneum thickness, a normal or prominent granular layer and increased mitoses. Development of skeletal features in this condition can be explained by the fact that the maintenance of healthy skeleton requires vitamin D, the main source of which is biosynthesis in the skin. Epidermal hyperproliferation disturbs this synthesis and results in rickets.

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. We herein describe a patient with ARCI who carried a homozygous nonsense mutation in the SDR9C7 gene and presented with generalized erythroderma, scales, recurrent blisters, and onychomycosis. 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 in SDR9C7 (c.187C&gt;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 a SDR9C7 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 by SDR9C7 mutation, and the unusual blisters further expand the clinical phenotypic spectrum of ARCI.

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis.

Mutations in genes such as transglutaminase-1 (TGM1), which are responsible for the formation and normal functioning of a lipid barrier, lead to the development of autosomal recessive congenital ichthyosis (ARCI). ARCIs are characterized by varying degrees of hyperkeratosis and the presence of scales on the body surface since birth. The quality of life of patients is often significantly affected, and in order to alleviate the manifestations of the disease, symptomatic therapy with moisturizers, keratolytics, retinoids and other cosmetic substances is often used to improve the condition of the patients’ skin. Graft transplantation is commonly used to correct defects of the eye. However, these approaches offer symptomatic treatment that does not restore the lost protein function or provide a long-term skin barrier. Gene and cell therapies are evolving as promising therapy for ARCIs that can correct the functional activity of altered proteins. However, these approaches are still at an early stage of development. This review discusses current studies of gene and cell therapy approaches for various types of ichthyosis and their further prospects for patient treatment.

Structural and functional foot disorders in patients with genodermatoses: a single-centre, retrospective chart review

BackgroundSkin lesions on the feet and foot deformities impair daily activities and decrease quality of life. Although substantial foot deformities occur in many genodermatoses, few reports have been published on this topic. Therefore, we performed a retrospective chart review to identify patients with genodermatoses and foot disorders. We included 16 patients, who were investigated clinically and with molecular biology.ResultsThe following genodermatoses with foot deformities were detected: autosomal recessive congenital ichthyosis (ARCI, n = 7); palmoplantar keratodermas (PPKs, n = 6); ichthyosis follicularis, atrichia, and photophobia (IFAP, n = 1); ectrodactyly-ectodermal dysplasia-clefting (EEC, n = 1); and ichthyosis with confetti (IWC, n = 1). Foot problems not only varied in severity depending on the disease but also showed phenotypic heterogeneity among patients with the same condition. Foot deformities were most pronounced in patients with EEC (split foot) or IWC (contractures) and less severe in those with ARCI (clawed toes), IFAP (hollow feet), or PPK (no bone abnormalities in the feet).ConclusionBecause a range of distinct genodermatoses involve foot abnormalities, early rehabilitation and other corrective measures should be provided to patients with foot involvement to improve gait and prevent/delay irreversible complications.

Nail involvement in autosomal recessive congenital ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a clinically and genetically heterogeneous category of nonsyndromic ichthyosis. Nail changes in ARCI are generally frequent but have been rarely reported and studied in the literature. This stimulated us to conduct a study to describe nail changes in ARCI using a combined literature review and prospective examination from March 2019 to August 2019 (6 months) in the Dermatology Department of Habib Thameur Hospital, Tunis, Tunisia. A total of 25 patients with ARCI had a clinical and dermatoscopic review. The mean age was 19.8 years (range, 1-43), with a female predominance (17 women [68%] and 8 men [32%]). Seventy-two percent had nail unit changes involving more than one nail, none had single nail disease, 64% had involvement of fingernails, and 68% had involvement of toenails, with cases including periungual hyperkeratosis (64%), xanthonychia (40%), pachyonychia (40%), macrolunula (36%), digital clubbing (32%), and onychomycosis (24%). Rarer findings included pseudoainhum, transverse leukonychia, longitudinal melanonychia, and subungual hemorrhages, each in one patient (4%). There was a statistically significant increased frequency of nail changes in adults over children (P = .001). Nail abnormalities statistically associated with ARCI were macrolunula, periungual hyperkeratosis, xanthonychia, and pachyonychia. A comprehensive review of the literature was performed, creating the first comprehensive review addressing nail disease in ARCI.

Erythroderma in a neonate

Erythroderma in a neonate

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal-recessive congenital ichthyosis.

Autosomal-recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self-improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non-SICI patients (nSICI, n = 60) by their ARCI phenotype. Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi-squared and t-Tests. The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo-/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo-/anhidrosis or vitamin D levels and monitored for changes in quality of life.

Whole‐exome sequencing identified a novel pathogenic mutation of the CYP4F22 gene in a Chinese patient with autosomal recessive congenital ichthyosis and in vitro study of the mutant CYP4F22 protein

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of rare cornification disorders. Of the 14 genes already known to cause ARCI, CYP4F22 is a relatively new genetic etiology, the mutation spectrum of which has yet to be profiled. Using whole-exome sequencing in family trios, we identified the compound heterozygous mutations, c.844C>T (p.R282W) and c.1189C>T (p.R397C), of the CYP4F22 gene (NM_173483.4) in a Chinese neonatal boy with a congenital ichthyosis phenotype. In combination with multiple in silico analyses and the following in vitro functional studies, we provided evidence to classify these two variations as pathogenic mutations and demonstrated that both variants significantly reduced the CYP4F22 protein amount. Interestingly, the reduction of both mutant CYP4F22 protein could be recovered by trichostatin A (TSA) treatment, suggesting some deacetylation factors involved in regulating the mutant CYP4F22 protein and implying TSA might be a potential candidate compound for congenital ichthyosis caused by CYP4F22 variations.

Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: genotype\u2013phenotype correlation

BackgroundIchthyosis is a heterogeneous group of Mendelian cornification disorders that includes syndromic and non-syndromic forms. Autosomal Recessive Congenital Ichthyosis (ARCI) and Ichthyosis Linearis Circumflexa (ILC) belong to non-syndromic forms. Syndromic ichthyosis is rather a large group of heterogeneous diseases. Overlapping phenotypes and genotypes between these disorders is a major characteristic. Therefore, determining the specific genetic background for each form would be necessary.MethodsA total of 11 Tunisian patients with non-syndromic (8 with ARCI and 2 with ILC) and autosomal syndromic ichthyosis (1 patient) were screened by a custom Agilent HaloPlex multi-gene panel and the segregation of causative mutations were analyzed in available family members.ResultsClinical and molecular characterization, leading to genotype–phenotype correlation in 11 Tunisian patients was carried out. Overall, we identified 8 mutations in 5 genes. Thus, in patients with ARCI, we identified a novel (c.118T > C in NIPAL4) and 4 already reported mutations (c.534A > C in NIPAL4; c.788G > A and c.1042C > T in TGM1 and c.844C > T in CYP4F22). Yellowish severe keratoderma was found to be associated with NIPAL4 variations and brachydactyly to TGM1 mutations. Two novel variations (c.5898G > C and c.2855A > G in ABCA12) seemed to be features of ILC. Delexon13 in CERS3 was reported in a patient with syndromic ichthyosis.ConclusionsOur study further extends the spectrum of mutations involved in ichthyosis as well as clinical features that could help directing genetic investigation.

Harlequin Ichthyosis: Folklore of Demon

Background: Harlequin ichthyosis (HI) is a severe and rare autosomal recessive congenital ichthyosis, characterized by severe hyperkeratosis, extensive fissuring and massive, diamond-shaped scales which limit the child’s movements. The term harlequin comes from the baby’s facial expression and diamond-shaped pattern of the scales like the 17th century entertainers, harlequins. The underlying genetic abnormality has been identified as a mutation in the lipid-transporter gene ABCA 12 on chromosome 2q35. Aim and objectives: To provide a comprehensive knowledge of severe forms of congenital ichthyosis, the harlequin ichthyosis and abolish the superstitious notion regarding the appearance of the neonate. Materials and Methods: The present report is case of premature girl baby delivered at MIMS, Mandya. The neonate presented plaques of rigid fixed skin, separated by deep red fissures, facial features were obliterated by thickened skin, undeveloped nose and pinna, severe ectropion and eclabium. Intensive care was given and survival was prolonged by systemic retinoids. The neonate succumbed to respiratory failure few days later. Results and conclusion: The present study gives a comprehensive knowledge of harlequin ichthyosis and provides emphasis on sensitization of the disease to prevent any misconception or superstition. Also lays emphasis on Genetic counseling of the couple to prevent further occurrences. KEY WORDS: Eclabium, Ectropion, Harlequin ichthyosis.

A case of autosomal recessive congenital ichthyosis with a novel mutation identified in the TGM1 gene by whole exome sequencing

Background: The &amp;quot;autosomal recessive congenital ichthyosis (ARCI)&amp;quot; refers to a group of rare, heterogeneous, and non-syndromic disorders of keratinization, represented as abnormal scales over the entire body and attributable to defective epidermal keratinocyte differentiation and lipid metabolism. ARCI is caused by mutations in a wide variety of genes, including ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4, TGM1, CERS3, PNPLA1, CASP14, SDR9C7, and SULT2B1. The most common cause of ARCI is a TGM1 gene mutation, which is strongly associated with a collodion membrane at birth. Case presentation: A 15-year-old male patient presented with extensive scaling over the entire body since birth. His history revealed that he was born ash-colored in a membrane, kept in an incubator for one month, and clinically diagnosed with ichthyosis at birth. The patient, who had undergone no previous genetic testing, was subjected to whole exome sequencing with the preliminary diagnosis of autosomal recessive/X-linked recessive congenital ichthyosis. The analysis identified a homozygous c.1020delG change in the TGM1 gene in the form of a frameshift mutation that is classified as pathogenic according to the American College of Medical Genetics criteria. Conclusion: Next-generation sequencing technologies employing whole-exome sequencing enable the sequencing of all protein-coding DNA regions in a single run.