MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases

Gillian S. Townend, Friederike Ehrhart*, Henk J. van Kranen, Mark Wilkinson, Annika Jacobsen, Marco Roos, Egon L. Willighagen, David van Enckevort, Chris T. Evelo, Leopold M. G. Curfs

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data.

Original languageEnglish
Pages (from-to)914-924
Number of pages11
JournalHuman Mutation
Volume39
Issue number7
DOIs
Publication statusPublished - Jul 2018

Keywords

  • databases
  • FAIR data
  • genetic variation
  • MECP2
  • phenotype
  • Rett syndrome
  • INTELLECTUAL DISABILITY
  • MUTATION DATABASE
  • GENOMIC VARIATION
  • HUMAN-DISEASE
  • VARIANTS
  • HUMANS
  • BIOINFORMATICS
  • RESOURCES
  • BIOBANKS
  • UPDATE

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