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FMRP expression studies in blood and hair roots in a fragile X family with methylation mosaics
  1. B B A de Vries1,
  2. L-A Severijnen2,
  3. A Jacobs1,
  4. R Olmer2,
  5. D J J Halley2,
  6. B A Oostra2,
  7. R Willemsen2
  1. 1Department of Human Genetics, University Medical Centre Nijmegen, The Netherlands
  2. 2Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands
  1. Correspondence to:
 Dr B B A de Vries, Department of Clinical Genetics, University Medical Centre Nijmegen, P O Box 9101, 6500 HB Nijmegen, The Netherlands; 
 b.devries{at}antrg.umcn.nl

https://doi.org/10.1136/jmg.40.7.535

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    The fragile X syndrome is a common cause of familial mental retardation with an estimated prevalence of 1/4000-1/6000 for males in western countries.1–3 This X linked disorder is characterised by mental retardation with additional features like a long face with large protruding ears, macro-orchidism, and eye gaze avoidance.4–6 The causative mutation is an amplification of a trinucleotide (CGG) repeat in the 5′ UTR of the FMR1 gene. Normal people have between six and 54 CGG repeats, carriers of the premutation have between 55 and 200, and affected subjects have more than 200 CGG repeats in their FMR1 gene, the so called full mutation.7,8 The latter expansion is accompanied by hypermethylation of the repeat and its upstream region resulting in a shutdown of transcription and absence of the FMRP.9–11

    In fragile X patients, two special subclasses of mosaicism can be distinguished on the basis of size and methylation pattern: (1) subjects with a premutation in a proportion of their cells in addition to a full mutation, often referred to as “size mosaics”; this pattern can be observed in 20–40% of male patients12,13; (2) subjects with intercellular variations in the methylation status of a full mutation, “methylation mosaics”.14 In a large multicentre study, “methylation mosaicism” was observed in 3% of the males with a full mutation.12

    Key points

    • In fragile X patients two special subclasses of mosaicism can be distinguished on the basis of size and/or methylation pattern: patients with full mutation and premutation, called “size mosaics”, and patients with intercellular variations of the methylation status, called “methylation mosaics”.

    • Within a known fragile X family, three brothers with methylation mosaic patterns were studied using the FMRP antibody test on both blood smears and hair roots. The index patient aged …

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