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Zinc finger 81 (ZNF81) mutations associated with X-linked mental retardation
  1. T Kleefstra1,
  2. H G Yntema1,
  3. A R Oudakker1,
  4. M J G Banning1,
  5. V M Kalscheuer2,
  6. J Chelly3,
  7. C Moraine4,
  8. H-H Ropers2,
  9. J-P Fryns5,
  10. I M Janssen1,
  11. E A Sistermans1,
  12. W N Nillesen1,
  13. L B A de Vries1,
  14. B C J Hamel1,
  15. H van Bokhoven1
  1. 1Department of Human Genetics, University Medical Centre St Radboud, Nijmegen, The Netherlands
  2. 2Max Planck Institute for Molecular Genetics, Berlin, Germany
  3. 3Département de Génétique et Pathologie Moléculaire, Institut Cochin (IC), Paris
  4. 4Unité de Génétique, CHU Bretonneau, Tours, France
  5. 5Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium
  1. Correspondence to:
 T Kleefstra
 Department of Human Genetics 417, UMC St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands; T.Kleefstraantrg.umcn.nl

https://doi.org/10.1136/jmg.2003.016972

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    X-linked mental retardation (XLMR) has a prevalence of 2.6 cases per 1000 population, accounting for over 10% of all cases of mental retardation. Clinically, XLMR exists in syndromic (MRXS) and non-syndromic (MRX) forms, that is without other distinguishing features.

    Non-syndromic X-linked mental retardation (MRX) is a highly heterogeneous group of conditions in which mental retardation (MR) is the only consistent clinical feature in patients. This in contrast to syndromic forms of X-linked mental retardation (MRXS), where MR is associated with recognisable clinical signs such as congenital malformations, neurological features, or metabolic disturbances. Identifying novel genes that are responsible for MRX is difficult due to the heterogeneity of this disorder. At present 30 genes have been identified as playing a role in MRXS. However in MRX, only 15 genes are known to be involved accounting for less than one-fifth of all MRX.1–6 The recent observations that RSK2, MECP2, and ARX play a role in both syndromic and non-syndromic forms of XLMR,7–10 suggest that a molecular basis to strictly separate these two forms is not always present. In addition, careful clinical re-examination of patients with an OPHN1 gene mutation has revealed distinctive phenotypic hallmarks, such as cerebellar hypoplasia, in patients who were previously classified as non-syndromic.11,12

    The frequency of causative mutations in any of the 15 MRX genes known today appears to be very low, so in the majority of patients with MRX the genetic cause is still not known. It has been suggested that up to 100 different genes might be involved in MRX.1–4 Seven of the 15 genes have been cloned on the basis of their disruption by chromosomal rearrangements in mentally retarded patients. Recently, it has been predicted that approximately 30% of all mutations underlying MRX are located in the …

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    Footnotes

    • This work was supported by grants from ZonMw (grant 940-37-031) the Dutch Brain Foundation (grant 10F02(2)43), and by an EU grant (QLG3-CT-2002-01810, Euro-MRX).

    • Conflicts of interest: none declared.