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Microdeletion in the FMR-1 gene: an apparent null allele using routine clinical PCR amplification
  1. Madhuri R Hegdea,
  2. Belinda Chonga,
  3. Matthew Fawknera,
  4. Nikolas Lambirisb,
  5. Hartmut Petersb,
  6. Aileen Kennesonc,
  7. Stephen T Warrenc,
  8. Donald R Loved,
  9. Julie McGaughrane
  1. aMolecular Genetics Laboratory, Auckland Hospital, Auckland, New Zealand, bInstitute of Medical Genetics, Medical School Charite, Humboldt University, D-10098 Berlin, Germany, cHoward Hughes Medical Institute, Emory University School of Medicine, 1510 Clifton Road, Room 4035 Rollins Research Center, Atlanta, Georgia 30322, USA, dMolecular Genetics and Development Group, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand, eNorthern Regional Genetics Service, Building 18, Auckland Hospital, Park Road, Grafton, Auckland, New Zealand
  1. Dr McGaughran JulieMc{at}ahsl.co.nz

https://doi.org/10.1136/jmg.38.9.624

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    Editor—Fragile X syndrome is the most common chromosomal cause of inherited mental retardation. At the chromosome level, this syndrome is characterised by the presence of a fragile site at Xq27.3.1 The incidence of this disorder is approximately 1 in 4000 and 1 in 7000 in males and females, respectively.2 3 In most cases, the mutation responsible for fragile X syndrome is a CGG repeat expansion in the 5′ untranslated region (UTR) of exon 1 of the FMR-1 gene. People in the normal population have six to approximately 50 repeats.4 5 Those with 50 to 200 repeats correspond to the premutation class. Repeats in this class are meiotically unstable and can expand to a full mutation.4 The premutation class encompasses the “grey area” of 45-55 CGG repeats for which there is a variable risk of repeat expansion.6 Subjects with a full mutation have repeat lengths in excess of 200, which are associated with hypermethylation of the CpG island immediately upstream of theFMR-1 gene.7-9 This methylation correlates with transcriptional suppression of theFMR-1 gene, while the repeat expansion has been suggested to cause translational suppression by impeding the migration of the 40S ribosomal subunit along the 5′ UTR of theFMR-1 gene transcript.9-11

    Fragile X syndrome has also been found to occur in a few patients without CGG repeat expansions. These mutation events fall into two classes, intragenic point mutations12 13 and deletion events.14-22 Of the latter class, five patients with microdeletions in the 5′ UTR of the FMR-1gene transcript have been described.23 24

    We report here a patient referred for fragile X testing who was found to carry an apparent null allele by PCR amplification of the CGG repeat region of the FMR-1 gene. This patient was …

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