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Genotype-phenotype correlations in FSHD

Authors
  • Zernov, Nikolay
  • Skoblov, Mikhail
Type
Published Article
Journal
BMC Medical Genomics
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Mar 13, 2019
Volume
12
Issue
Suppl 2
Identifiers
DOI: 10.1186/s12920-019-0488-5
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundFacial-scapular-humeral myodystrophy Landouzy-Dejerine (FSHD) is an autosomal dominant disease, the basis of its pathogenesis is ectopic expression of the transcription factor DUX4 in skeletal muscle. There are two types of the disease: FSHD1 (MIM:158900) and FSHD2 (MIM: 158901), which have different genetic causes but are phenotypically indistinguishable. In FSHD1, partial deletion of the D4Z4 repeats on the 4th chromosome affects the expression of DUX4, whereas FSHD2 is caused by the mutations in the protein regulating the methylation status of chromatin - SMCHD1. High variability of clinical picture, both intra - and inter-family indicates a large number of factors influencing clinical picture. There are key genetic, epigenetic and gender factors that influence the expressivity and penetrance of the disease. Using only one of these factors allows just a rough prediction of the course of the disease, which indicates the combined effect of all of the factors on the DUX4 expression and on the clinical picture.ResultsIn this paper, we analyzed the impact of genetic, epigenetic and gender differences on phenotype and the possibility of using them for disease prognosis and family counselling.ConclusionsKey pathogenesis factors have been identified for FSHD. However, the pronounced intra - and inter-family polymorphism of manifestations indicates a large number of modifiers of the pathological process, many of which remain unknown.

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