Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males
- V Cantagrel1,*,
- A-M Lossi1,*,
- S Boulanger2,
- D Depetris1,
- M-G Mattei1,
- J Gecz3,
- C E Schwartz4,
- L Van Maldergem2,
- L Villard1
- 1Inserm U491, Faculté de Médecine de La Timone, 27, Bd. Jean Moulin, 13385 Marseille Cedex 5, France
- 2Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Loverval, Belgium
- 3Department of Genetic Medicine, Women and Children’s Hospital, Adelaide, Australia
- 4Greenwood Genetic Center, One Gregor Mendel Circle, Greenwood, SC, USA
- Correspondence to: Lionel Van Maldergem Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Allée des Templiers, 41, B-6280 Loverval, Belgium;
- Received 14 May 2004
- Accepted 20 May 2004
Background: Mental retardation (MR) affects 2–3% of the human population and some of these cases are genetically determined. Although several genes responsible for MR have been identified, many cases have still not been explained.
Methods: We have identified a pericentric inversion of the X chromosome inv(X)(p22.3;q13.2) segregating in a family where two male carriers have severe MR while female carriers are not affected.
Results: The molecular characterisation of this inversion led us to identify two new genes which are disrupted by the breakpoints: KIAA2022 in Xq13.2 and P2RY8 in Xp22.3. These genes were not previously fully characterised in humans. KIAA2022 encodes a protein which lacks significant homology to any other known protein and is highly expressed in the brain. P2RY8 is a member of the purine nucleotide G-protein coupled receptor gene family. It is located in the pseudo-autosomal region of the X chromosome and is not expressed in brain.
Conclusions: Because the haploinsufficiency of P2RY8 in carrier mothers does not have a phenotypic consequence, we propose that the severe MR of the affected males in this family is due to the absence of the KIAA2022 gene product. However, screening 20 probands from X linked MR families did not reveal mutations in KIAA2022. Nonetheless, the high expression of this gene in fetal brain and in the adult cerebral cortex could be consistent with a role in brain development and/or cognitive function.
- AR, androgen receptor
- BrdU, 5-bromodeoxyuridine
- FISH, fluorescent in situ hybridisation
- MR, mental retardation
- NS MR, non-syndromic mental retardation
- NS XLMR, non-syndromic X linked mental retardation
- PAR1, pseudoautosomal region 1
↵* These two authors contributed equally to this work.
Financial support to VC from the French Ministry of Research is gratefully acknowledged. This study was supported in part by a grant from NICHD (HD26202) to CES.
Conflict of interest: none declared.