Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosisReportar como inadecuado

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Orphanet Journal of Rare Diseases

, 11:4

Rare skin diseases


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.

KeywordsIchthyosis Multidisciplinary approach Molecular diagnosis AbbreviationsNGSNext-generation sequencing

ARCIAutosomal recessive congenital ichthyosis

LILamellar ichthyosis

CEICongenital ichthyosiform erythroderma

TSCATruSeq Custom Amplicon

DSDesign Studio

RTAReal Time Analysis

GATKGenome Analysis Toolkit

AVAmplicon Viewer

IGVIntegrative Genome Viewer

aCGHArray Comparative Genomic Hybridization


MEDNIKMental retardation-enteropathy-deafness-neuropathy-ichthyosis-keratoderma

CEDNIKCerebral dysgenesis-neuropathy-ichthyosis-palmoplantar keratoderma

Andrea Diociaiuti and May El Hachem contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13023-016-0384-4 contains supplementary material, which is available to authorized users.

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Autor: Andrea Diociaiuti - May El Hachem - Elisa Pisaneschi - Simona Giancristoforo - Silvia Genovese - Pietro Sirleto - Renata Bo


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