Molecular Epidemiology of Hereditary Epidermolysis Bullosa in a Middle Eastern Population (original) (raw)
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Genetic Profile of Epidermolysis Bullosa Cases in King Abdulaziz Medical City, Riyadh, Saudi Arabia
Frontiers in Genetics, 2021
Epidermolysis bullosa (EB) is a rare heterogeneous genetic mechanobullous skin disorder that is characterized by increased skin fragility leading to blistering following minor trauma. EB may be inherited as an autosomal dominant or an autosomal recessive disorder and can be classified into dystrophic EB (DEB), junctional EB (JEB), and EB simplex (EBS). A total of 28 Saudi patients with EB were included in this observational, retrospective chart-review study. A consecutive non-probability sampling technique was used to approach all affected patients. Molecular analysis was done to test the patients’ genomic DNA using a custom-designed AmpliSeq panel of suspected genes. All disease-causing variants were checked against available public databases. Twelve patients (42.9%) were found to have DEB, 6 patients (21.4%) with JEB, and 10 patients (35.7%) with EBS. The molecular genetic results revealed detections of 24 various homozygous genetic variations in the genes associated with EB, of w...
Clinical subtypes and molecular basis of epidermolysis bullosa in Kuwait
International journal of dermatology, 2018
Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous blistering skin disease, but in countries such as Kuwait, there are very limited data on the clinical and molecular pathology of EB. To improve understanding of EB in Kuwait, we report the experience of a local tertiary referral center over a 17.5 year period (January 2000-June 2017) in establishing clinical and molecular diagnoses. Review of hospital records and diagnostic reports. Individual cases were diagnosed by combinations of clinical assessment, skin biopsy (immunohistochemistry and transmission electron microscopy), Sanger sequencing of EB genes, and whole exome sequencing. Fifty-four families with EB were registered with the clinic over this period, 41 of whom (84 patients) participated in diagnostic studies. Thirty-seven of these 41 families had consanguineous marriages; 34 had recessive forms of EB, while only seven had dominant subtypes. Recurrent mutations were observed in epidermal dystonin, tran...
Journal of The American Academy of Dermatology, 2002
Background: Junctional epidermolysis bullosa (JEB) is a group of inherited blistering diseases characterized by epidermal-dermal separation resulting from mutations that affect the function of critical components of the basement membrane zone. This group of autosomal recessive diseases is especially prevalent in regions where consanguinity is common, such as the Middle East. However, the clinical and genetic epidemiology of JEB in this region remains largely unexplored. Objective: The aim of the present study was to assess a series of consanguineous JEB families originating from the Middle East. Methods: We identified 7 families referred to us between 1998 and 1999 and originating from the United Arab Emirates, Saudi Arabia, Sudan, Yemen, and Israel. Histologic, immunofluorescence, and electron microscopy studies were performed to direct the subsequent molecular analysis. DNA obtained from all family members was amplified by means of polymerase chain reaction and analyzed by conformation-sensitive gel electrophoresis with subsequent direct sequencing. Results: In 6 families presenting with the clinical and histologic features distinctive for JEB, mutations in genes encoding 1 of the 3 subunit polypeptides of laminin-5 were identified. Two families each had mutations in LAMB3, 2 in LAMA3, and 2 in LAMC2. Out of 7 distinct mutations, 5 were novel and 2 were recurrent. No relationship was found between the presence of nonsense/frameshift mutations in laminin-5 genes and perinatal mortality, contradicting a major genotype-phenotype correlation previously reported in the European and US literature. Similarly, none of the recurrent LAMB3 hot spot mutations previously described in other populations was found in our series. Finally, in a family with the clinical diagnosis of generalized atrophic benign epidermolysis bullosa, a homozygous non-sense mutation in Col17A1 gene (encoding the BPAG2 antigen) was identified. Conclusion: The present report suggests (1) the existence of a unique spectrum of mutations in the Middle East populations and (2) the need for the implementation of a diagnostic strategy tailored to the genetic features of JEB in this region. (J Am Acad Dermatol 2002;46:510-6.)
Journal of the European Academy of Dermatology and Venereology : JEADV, 2014
Epidermolysis bullosa (EB) is a rare and so far incurable genetic disease, affecting mainly the skin and mucosal membranes, manifesting with blisters triggered by minor mechanical trauma. Since only few epidemiological data on EB are available, we established a Registry for EB and implemented molecular diagnostic methods. We present epidemiologic data from the EB Registry and genotype-phenotype correlations. In 2006, a registry of patients with EB was initiated in the Department of Dermatology of the University of Medicine, as well as molecular diagnostic tools. The patients were diagnosed on clinical bases, and whenever possible, immunofluorescence mapping and molecular analysis were performed. 89 EB patients were enrolled in the study from 2006 to 2012: 58 patients with dystrophic EB (DEB), 20 with EB simplex, one patient was diagnosed with Kindler syndrome; in 10 patients, the type of EB could not be determined. We have estimated, the total number of EB patients in Romania and we...
Molecular genetic assays for inherited epidermolysis bullosa
Clinics in Dermatology, 2011
Epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders, characterized by blistering of skin and mucosal membranes under normal mechanical stress conditions. The clinical phenotype ranges from mild localized to severe generalized disease with secondary extracutaneous symptoms and premature death. The lives of the patients and their families are marked by this disorder, causing severe physical, psychologic, and material burdens. The four major EB types are classified by the level of skin blistering, but more than 30 subtypes can be distinguished, according to clinical and molecular genetic criteria. So far, mutations in 14 genes are known to cause different EB subtypes. The diagnosis of the EB subtype is essential for the prognosis, genetic counseling, and prenatal diagnosis. Because the symptoms are often overlapping or not specific, the diagnosis of the EB type is usually not possible by clinical criteria or routine histologic examination. Immunofluorescence analysis of skin sections with antibodies to proteins of the basement membrane zone is the first diagnostic step to indicate the level of skin split and the missing protein. Mutation analysis indicates the precise cause of the disease, the affected gene, and the inheritance pattern.
Epidermolysis Bullosa—A Different Genetic Approach in Correlation with Genetic Heterogeneity
Diagnostics
Epidermolysis bullosa is a heterogeneous group of rare genetic disorders characterized by mucocutaneous fragility and blister formation after minor friction or trauma. There are four major epidermolysis bullosa types based on the ultrastructural level of tissue cleavage: simplex, junctional, dystrophic, and Kindler epidermolysis bullosa. They are caused by mutations in genes that encode the proteins that are part of the hemidesmosomes and focal adhesion complex. Some of these disorders can be associated with extracutaneous manifestations, which are sometimes fatal. They are inherited in an autosomal recessive or autosomal dominant manner. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in epidermolysis bullosa, and on the correlation genotype–phenotype.
Journal of the American Academy of Dermatology, 2008
Background: Since publication in 2000 of the Second International Consensus Report on Diagnosis and Classification of Epidermolysis Bullosa, many advances have been made to our understanding of this group of diseases, both clinically and molecularly. At the same time, new epidermolysis bullosa (EB) subtypes have been described and similarities with some other diseases have been identified. Objective: We sought to arrive at a new consensus of the classification of EB subtypes. Results: We now present a revised classification system that takes into account the new advances, as well as encompassing other inherited diseases that should also be included within the EB spectrum, based on the presence of blistering and mechanical fragility. Current recommendations are made on the use of specific diagnostic tests, with updates on the findings known to occur within each of the major EB subtypes. Electronic links are also provided to informational and laboratory resources of particular benefit to clinicians and their patients. Limitations: As more becomes known about this disease, future modifications may be needed. The classification system has been designed with sufficient flexibility for these modifications. Conclusion: This revised classification system should assist clinicians in accurately diagnosing and subclassifying patients with EB.
Genotypic Heterogeneity and the Mode of Inheritance in Epidermolysis Bullosa
Epidermolysis bullosa (EB) comprises a clinically heterogeneous group of disorders characterized by fragility of skin, leading to formation of blisters, erosions, and chronic ulcers. The cutaneous manifestations, together with extracutaneous complications, cause considerable morbidity and in some cases premature death.1,2 Epidermolysis bullosa is an orphan disease (defined in the United States as a diagnosis with < 200 000 affected individuals), yet there are up to 40 000 affected individuals in the United States and as many as half a million patients globally. The disease is characteristically diagnosed at birth or during the early postnatal period, and there is currently no effective and specific treatment beyond prevention of trauma, appropriate wound care, and prevention of infections. Thus, EB imposes a major burden for global health care, and the cost of the treatment of a severely affected patient in the United States can approach $300 000 per year ( email communication; November 24, 2015; Brett Kopelan, executive director of the dystrophic epidermolysis bullosa research association [DEBRA] of America).
Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification
Journal of the American Academy of Dermatology, 2014
Background: Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described.