Abstract
BackgroundThe term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. Mutations in a broad group of genes related to keratinocyte differentiation and epidermal barrier function have been demonstrated to play a causative role in disease development. Ichthyosis may be classified in syndromic or non-syndromic forms based on the occurrence or absence of extracutaneous signs. In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing.MethodsDue to the complex features of the different ichthyoses and the high number of genes involved we have investigated a group of 64 patients, affected by syndromic and non-syndromic diseases, using Next Generation Sequencing as a new tool for the molecular diagnosis.ResultsUsing this innovative molecular approach we were able to find pathogenic mutations in 53 out of 64 patients resulting in 82.8 % total detection rate. An interesting result from the analysis of the data is the high rate of novel sequence variations found compared to known mutations and the relevant rate of homozygous mutations.ConclusionsThe possibility to analyze a large number of genes associated with various diseases allows to study cases with phenotypes not well-determined, giving the opportunity to make new genotype-phenotype correlation. In some cases there were discrepancies between clinical features and histology or electron microscopy and only molecular analysis allowed to definitively resolve the diagnostic dilemma. The genetic diagnosis of ichthyosis leads to a more accurate and effective genetic counseling, allowing correct evaluation of the risk of recurrence, particularly in families with consanguineous background.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0384-4) contains supplementary material, which is available to authorized users.
Highlights
The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions
Non syndromic forms are divided in common ichthyoses, autosomal recessive congenital ichthyosis (ARCI), keratinopathic ichthyoses and others
For the syndromic genes: ALDH3A2 and MBTPS2 were fully covered by Next-Generation Sequencing (NGS) analysis; PHYH, PEX7, SNAP29, AP1S1, SPINK5 and EBP had only one region to be sequenced by Sanger, while VPS33B six regions
Summary
The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. Ichthyosis may be classified in syndromic or non-syndromic forms based on the occurrence or absence of extracutaneous signs. In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing. The classification of Oji et al in 2010 has divided the various forms of ichthyosis in two major groups, non-syndromic and syndromic, on the basis of the absence or presence of extracutaneous symptoms [1]. The latter are classified according to the prevalent symptom. Non syndromic forms are divided in common ichthyoses (vulgaris and X-linked), autosomal recessive congenital ichthyosis (ARCI), keratinopathic ichthyoses and others
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