J Med Genet 39:430-433 doi:10.1136/jmg.39.6.430
  • Letters to JMG

A novel 2 bp deletion in the TM4SF2 gene is associated with MRX58

  1. F E Abidi1,
  2. E Holinski-Feder2,
  3. O Rittinger3,
  4. F Kooy4,
  5. H A Lubs5,
  6. R E Stevenson1,
  7. C E Schwartz1
  1. 1J C Self Research Institute, Greenwood Genetic Center, Greenwood, SC, USA
  2. 2Medizinisch Genetisches Zentrum, Bayerstrasse 53, D-80335, Munchen, Germany
  3. 3Landeskrankenanstalten Salzburg, Kinderspital, Klinische Genetik, Salzburg, Austria
  4. 4Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
  5. 5Pediatrics/Genetic Division University of Miami, Miami, FL, USA
  1. Correspondence to:
 Dr C Schwartz, Center for Molecular Studies, J C Self Research Institute, One Gregor Mendel Circle, Greenwood, SC 29646, USA;

    X linked mental retardation (XLMR) represents around 5% of all MR, with a prevalence of 1 in 600 males.1,2 Fifteen to twenty percent of the total XLMR is the result of the fragile X syndrome.3 Non-fragile X mental retardation was subdivided into syndromal and non-syndromal conditions by Neri et al4 in 1991. The syndromal XLMR entities (MRXS) are those in which there is a specific pattern of physical, neurological, or metabolic abnormalities associated with the presence of mental retardation.5 Non-syndromic XLMR (MRX) are conditions in which a gene mutation causes mental retardation in the absence of other distinctive dysmorphic, metabolic, or neurological features.6 At present, XLMR conditions consist of 136 MRXS7 and 75 MRX8 entities. To date, 35 genes have been cloned. However, so far only nine non-syndromic XLMR genes have been identified: TM4SF2, FMR2, OPHN1 (MRX60), GDI1 (MRX41, MRX48), PAK3 (MRX30, MRX47), RSK2 (MRX19), IL1RAPL (MRX34), ARHGEF6 (MRX46), and MECP2 (MRX16).9–18

    TM4SF2, a member of the transmembrane 4 superfamily, maps to Xp11.4 and is one of the genes associated with non-syndromic XLMR.9 Mutations in TM4SF2 have been previously described in two families (L28 and T15) with non-syndromic XLMR. As a part of our XLMR candidate gene testing, we have screened probands from 14 XLMR families (10 linked to Xp11 and four small families with no linkage data) for mutations in the TM4SF2 gene. Here we report a novel 2 bp deletion (564delGT), which segregates with mental retardation in the MRX58 family. The deletion causes a frameshift and a subsequent stop codon six amino acids downstream (stop codon 192). This finding supports the hypothesis that different XLMR conditions, especially non-syndromic XLMR, result from mutations in the same gene.



    Probands from 14 XLMR families (three MRXS and …