Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males

V. Cantagrel, A. M. Lossi, S. Boulanger, D. Depetris, M. G. Mattei, J. Gecz, C. E. Schwartz, Lionel Van Maldergem, L. Villard

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages736-742
Number of pages7
JournalJournal of Medical Genetics
Volume41
Issue number10
DOIs
Publication statusPublished - 1 Oct 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Cantagrel, V. ; Lossi, A. M. ; Boulanger, S. ; Depetris, D. ; Mattei, M. G. ; Gecz, J. ; Schwartz, C. E. ; Van Maldergem, Lionel ; Villard, L. / Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. In: Journal of Medical Genetics. 2004 ; Vol. 41, No. 10. pp. 736-742.
@article{93cb805652274499b5c68af610a279c3,
title = "Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males",
abstract = "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.",
author = "V. Cantagrel and Lossi, {A. M.} and S. Boulanger and D. Depetris and Mattei, {M. G.} and J. Gecz and Schwartz, {C. E.} and {Van Maldergem}, Lionel and L. Villard",
year = "2004",
month = "10",
day = "1",
doi = "10.1136/jmg.2004.021626",
language = "English",
volume = "41",
pages = "736--742",
journal = "Journal of medical genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "10",

}

Cantagrel, V, Lossi, AM, Boulanger, S, Depetris, D, Mattei, MG, Gecz, J, Schwartz, CE, Van Maldergem, L & Villard, L 2004, 'Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males', Journal of Medical Genetics, vol. 41, no. 10, pp. 736-742. https://doi.org/10.1136/jmg.2004.021626

Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. / Cantagrel, V.; Lossi, A. M.; Boulanger, S.; Depetris, D.; Mattei, M. G.; Gecz, J.; Schwartz, C. E.; Van Maldergem, Lionel; Villard, L.

In: Journal of Medical Genetics, Vol. 41, No. 10, 01.10.2004, p. 736-742.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males

AU - Cantagrel, V.

AU - Lossi, A. M.

AU - Boulanger, S.

AU - Depetris, D.

AU - Mattei, M. G.

AU - Gecz, J.

AU - Schwartz, C. E.

AU - Van Maldergem, Lionel

AU - Villard, L.

PY - 2004/10/1

Y1 - 2004/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=6344265518&partnerID=8YFLogxK

U2 - 10.1136/jmg.2004.021626

DO - 10.1136/jmg.2004.021626

M3 - Article

VL - 41

SP - 736

EP - 742

JO - Journal of medical genetics

T2 - Journal of medical genetics

JF - Journal of medical genetics

SN - 0022-2593

IS - 10

ER -