Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Photoletter to the editor: Lamellar ichthyosis and arthrogryposis in a premature neonate.

ABSTRACT: Lamellar ichthyosis is a rare congenital disorder characterized by collodion membrane at birth and facial anomalies (eclabium and ectropion). The major underlying genetic defect is in TGM1, with mutations of this gene found in 50% of patients. An early diagnosis is fundamental in view of establishing a specific treatment due to the severity of the disease. We report a case of severe lamellar ichthyosis and arthrogryposis, without the typical facial presentation, negative for TGM1 mutations. The clinical improvement was achieved only after treatment with oral retinoids, highlighting the importance of early diagnosis and prompt administration of a specific therapy.

SUBMITTER: De Leonibus C

PROVIDER: S-EPMC4517804 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Photoletter to the editor: Lamellar ichthyosis and arthrogryposis in a premature neonate.

De Leonibus Chiara C Lembo Claudio C Santantonio Alfredo A Fioretti Tiziana T Rojo Silvana S Salvatore Francesco F De Vivo Massimiliano M Esposito Gabriella G Giliberti Paolo P

Journal of dermatological case reports 20150630 2

Lamellar ichthyosis is a rare congenital disorder characterized by collodion membrane at birth and facial anomalies (eclabium and ectropion). The major underlying genetic defect is in TGM1, with mutations of this gene found in 50% of patients. An early diagnosis is fundamental in view of establishing a specific treatment due to the severity of the disease. We report a case of severe lamellar ichthyosis and arthrogryposis, without the typical facial presentation, negative for TGM1 mutations. The ...[more]

PMID: 26236414

Similar Datasets

Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis.

Project description:Autosomal recessive lamellar ichthyosis is a severe congenital disorder of keratinization, characterized by variable erythema of the whole body surface and by different scaling patterns. Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2. We have now analyzed the genotype/phenotype correlation in a total of 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage to this locus revealed seven different missense mutations, five of these unpublished so far, and one splice mutation. No genotype/phenotype correlation for mutations in the TGM1 gene was found in this group of patients, which included two unrelated patients homozygous for the same mutation. Similarly, no clear difference in the clinical picture was seen between patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications for patients with lamellar ichthyosis shows no consistency and thus indicates that clinical criteria currently in use cannot discriminate between the molecularly different forms of the disease.

| S-EPMC1377076 | biostudies-other

Transglutaminase-1 mutations in Omani families with lamellar ichthyosis.

Project description:ObjectiveTo determine the molecular basis of familial ichthyosis in three Omani families.Subjects and methodsNine patients from three consanguineous families, A, B, and C, were born with typical features of lamellar ichthyosis subtype including collodion membrane and maintained ectropion, and epidermal scaling through their childhood. The 4 patients from family B had more severe symptoms requiring neonatal critical care and subsequent regular treatment with emollients, eye lubricants, and low-dose acitretin. DNA was extracted from peripheral blood by standard methods. The samples were initially genotyped to screen known loci linked to recessive ichthyosis on chromosomes 2q33-32 (ABCA12), 14q11 (TGM1), and 19p12-q12 using commercially supplied polymorphic fluorescent microsatellite markers. TGM1 was analyzed by direct sequencing for disease-associated mutations.ResultsTwo known pathogenic mutations in TGM1 were detected: p.Gly278Arg in families A and B and p.Arg396His in family C. These two mutations were segregating in an autosomal recessive mode of inheritance.ConclusionTwo known pathogenic TGM1 mutations were detected in three large consanguineous Omani families with lamellar ichthyosis. This study confirmed the geographic distribution of known mutations to an apparently unrelated population.

| S-EPMC5586776 | biostudies-literature

Minimal scarring in a premature neonate.

Project description:BackgroundScar formation and management is one of the major issues in plastic surgery. Scars are a chronic burden to patients, their families, and the wider healthcare system and while non-surgical and surgical options have been shown to reduce scarring and its impact, there are currently no therapeutic options to completely heal scars or to avoid scarring. Early gestation animals have been reported to heal skin wounds without scarring.Case presentationWe report on a premature, underweight-for-age neonate of 30 weeks' gestation that suffered a combination of deep partial thickness abrasions and full thickness wounds following birth trauma, who eventually healed with minimal skin scarring.ConclusionThis case highlights that more research is needed to understand the mechanism and timelines of foetal skin healing, so the knowledge can be used to develop better therapeutic options to treat skin scars in adults.

| S-EPMC10587665 | biostudies-literature

Somatosensory prediction in the premature neonate brain.

Project description:Sensory prediction (SP) is at the core of early cognitive development. Impaired SP may be a key to understanding the emergence of neurodevelopmental disorders, however there is little data on how and when this skill emerges. We set out to provide evidence of SP in the brain of premature neonates in the fundamental sensory modality: touch. Using Diffuse Correlation Spectroscopy, we measured blood flow changes in the somatosensory cortex of premature neonates presented with a vibrotactile stimulation-omission sequence. When ISI was fixed, participants presented a decrease in blood flow during stimulus omissions, starting when a stimulus should begin: the expectation of a certain stimulus onset induced deactivation of the somatosensory cortex. When ISI was jittered, we observed an increase in blood flow during omissions: the expectation of a likely but not certain stimulus onset induced activation of the somatosensory cortex. Our results reveal SP in the brain as early as four weeks before term, based on the temporal structure of a unimodal somatosensory stimulation, and show that SP produces opposite regulation of activity in the somatosensory cortex depending on how liable is stimulus onset. Future studies will investigate the predictive value of somatosensory prediction on neurodevelopment in this vulnerable population.

| S-EPMC9428805 | biostudies-literature

A cellular disease model towards gene therapy of TGM1-dependent Lamellar Ichthyosis

Project description:Lamellar Ichthyosis (LI) is a chronic disease, mostly caused by mutations in TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene edited cells showed complete absence of Transglutaminase-1 (TG1) expression and recapitulate a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a SINγ-RV vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity and cornified envelopes formation, hence restored proper epidermal architecture. Single cell multiomic analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial to epidermal regeneration. This study serves as a proof-of-concept for assessing the potential of this therapeutic approach in treating TGM1 dependent LI.

2024-07-29 | GSE268321 | GEO

A cellular disease model toward gene therapy of TGM1-dependent lamellar ichthyosis.

Project description:Lamellar ichthyosis (LI) is a chronic disease, mostly caused by mutations in the TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available, and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, such as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene-edited cells showed complete absence of transglutaminase 1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a self-inactivating γ-retroviral (SINγ-RV) vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity, and cornified envelope formation and, hence, restored proper epidermal architecture. Single-cell multiomics analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial for epidermal regeneration. This study serves as a proof of concept for assessing the potential of this therapeutic approach in treating TGM1-dependent LI.

| S-EPMC11372595 | biostudies-literature

An Extremely Premature Neonate with Severe Anemia.

Project description:Spleen rupture in an extremely premature newborn is very rare event. High index of suspicion is required to make timely diagnosis and thereafter appropriate management. We present a rare case of an extremely premature, extremely low birthweight newborn who presented with severe anemia secondary to splenic rupture. It was managed conservatively without splenectomy resulting in complete resolution of symptoms. Although non-operative management of pediatric splenic injuries is now recognized as the treatment of choice, there is very little experience in premature newborns.

| S-EPMC5538599 | biostudies-other

Congenital lamellar ichthyosis in Tunisia is caused by a founder nonsense mutation in the TGM1 gene.

Project description:Lamellar ichthyosis (LI, MIM# 242300) is a severe autosomal recessive genodermatosis present at birth in the form of collodion membrane covering the neonate. Mutations in the TGM1 gene encoding transglutaminase-1 are a major cause of LI. In this study molecular analysis of two LI Tunisian patients revealed a common nonsense c.788G>A mutation in TGM1 gene. The identification of a cluster of LI pedigrees carrying the c.788G>A mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a haplotype-based analysis by way of genotyping 4 microsatellite markers and 8 SNPs flanking and within the TGM1 gene spanning a region of 6 Mb. Haplotype reconstruction from genotypes of all members of the affected pedigrees indicated that all carriers for the mutation c.788G>A harbored the same haplotype, indicating common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counselling of affected LI pedigrees in Tunisia.

| S-EPMC3563951 | biostudies-literature

Ichthyosis in Sjogren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion.

Project description:Sjögren-Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren-Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum-stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren-Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.

| S-EPMC2892059 | biostudies-literature

Refractory Ileal Perforations in a Cytomegalovirus-Infected Premature Neonate Resolved After Ganciclovir Therapy.

Project description:Severe neonatal gastrointestinal diseases such as necrotizing enterocolitis or spontaneous intestinal perforation are potentially lethal conditions which predominantly occur in preterm infants. Cytomegalovirus (CMV), which is known to cause congenital and acquired infections in the newborns, has also been implicated in such severe gastrointestinal diseases in premature infants. However, the pathogenic role of CMV and effect of antiviral therapy in severe gastrointestinal disease in premature neonates is currently unclear. We present an infant, born at 26-weeks' gestation, presented with progressive dyspepsia and abdominal distention after the closure of the symptomatic patent ductus arteriosus at the day of life (DOL) 4, requiring the emergent surgery for ileal perforation at the DOL8. After the surgery, abdominal symptoms persisted and the second emergent surgery was performed for the recurrent ileal perforation at DOL17. Even then the abdominal symptoms prolonged and pathological examination in the affected intestine at the second surgery showed CMV inclusion body. Immunoreactivity for CMV antigen was detected in the specimen at the first surgery on DOL8. Blood and urinary CMV-DNA were detected at DOL28. CMV-DNA was also detected in the dried umbilical cord which was obtained within a week from birth. A 6-week course of intravenous ganciclovir (12 mg/kg/day) was started at DOL34 and then symptoms resolved along with decreasing blood CMV-DNA. Pathological findings characteristic of CMV were not detected in the resection specimen at the ileostomy closure at DOL94. These observations indicate that anti-CMV therapy may be beneficial for some premature infants with severe CMV-associated gastrointestinal diseases and warrants further studies focusing on pathogenic role, diagnosis, treatment and prevention of this underrecognized etiology of severe gastrointestinal diseases particularly in premature neonates.

| S-EPMC7372912 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data