Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex.
ABSTRACT Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes.
To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation.
Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing.
KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype.
This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.
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ABSTRACT: Hyperpigmentation is a key feature in a variety of inherited and acquired syndromes. Nonetheless, determining the exact diagnosis only on the clinical phenotype can be challenging and a detailed search for associated symptoms is often of crucial importance. As pigmentation pathways are regulated by complex signaling transduction cascades (e.g. MSH/cAMP, KIT signaling pathways), the underlying defects leading to elevated melanin production are numerous. With regard to treatment, limited therapeutic options exist, each with specific side-effects. In acquired hyperpigmentation, the melanin deposition may however be reversible after adequate therapy of the underlying disorder or even disappear spontaneously. In this review, we provide an overview of the biology of hyperpigmentation syndromes classified according to the main underlying defect that deregulates physiological melanogenesis. The identification of novel genes or key players involved in hyperpigmentary disorders is becoming increasingly important in view of the development of safer and more efficient treatments. This article is protected by copyright. All rights reserved.Pigment Cell & Melanoma Research 02/2014; · 5.84 Impact Factor
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ABSTRACT: Background: There are 72 families with epidermolysis bullosa (EB) in Romania. Since 2012 a National Program for the treatment of these patients is run by the Ministry of Health.The objectives of the strategies for EB patients are to optimize the management (diagnosis, treatment, monitoring) and to provide actual information on classification and patho-physiology which dictate the course of the disease.Methods: An international expert panel of specialists produced by consensus the recommendations for the management of EB cases in Romania taking into account the local possibilities. Patient association proposals were included. A review of the literature was performed to up-date the information.Outcomes: A strategy for diagnosis, treatment and follow-up of the patients with EB was elaborated in clear steps. Pharmacological treatments and wound care indications are provided together with a useful score for patient evaluation.Conclusion: These recommended strategies are allowing dermatologists to generate an individualized care plan for patients with EB.Mædica. 06/2013; 8(2):200-5.