Linkage analysis of six Algerian families with autosomal recessive non specific mental retardation

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Nadia Guessibia
Noureddine Sarrai
Nassima Methari
Bachir Ridouh
Habiba Chaabouni Bouhamed

Abstract

Background: Mental retardation is one of the most frequent major handicap, with a 1-3 % frequency in the general population. The recent progress of molecular biology and cytogenetic allowed to identify new genes for non syndromic autosomal recessive mental retardation.
Aim: To seek a genetic linkage to the loci implied in the nonspecific mental retardation transmitted into autosomal recessive (ARNSMR) in Algerian families with several affected members and to make the Genetic analysis of ARNSMR for 4 known loci: 3p25-pter; 4q24- q25, 19p13.12 and 1p21.1-p13.
Methods: The study concerned 34 individuals including 15 patients, belonging to six consanguineous Algerian families. Genotyping was made using polymorphic microsatellite markers and the analysis carried out thanks to the program Gene Mapper software. Statistical analyses were validated using the Fast Link programme of the Easy linkage software (V4:00 betas).
Results: The study carried out made it possible to exclude linkage of all loci for 3 families, nevertheless the linkage of one family to the locus 1p21.1-p13.3 remains possible.
Conclusion: The absence of linkage of 4 Algerian families with autosomal recessive mental retardation to 3 well known loci, confirms the genetic heterogeneity of mental retardation. We have to pursue research of candidate genes by whole genome scan.

Keywords:

Mental retardation, autosomal recessive, linkage analysis, Algeria, genotypin

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References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th.Ed. Washington DC: The American Psychiatric Association 1994.
  2. Shevell M, Ashwal S, Donley D, et al. Practice Committee of the Child Neurology Society. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Neurology. 2003;60:367-80.
  3. Rio M, Colleaux L, Sanlaville D, Borck G, Molinari F, Munnich A. Approches diagnostic chez les patients atteints de retard mental sévère et syndromique. Arch Pediatr. 2004 ;11:566-568.
  4. Chelly J. Retards mentaux liés au chromosome X. Médecine/Sciences 2000; 16 :363-367.
  5. Ropers HH, Hamel BC. X-Linked mental retardation. Nat Rev Genet. 2005;6:46-57. Review.
  6. Ropers HH. X-linked mental retardation: many genes for a complex disorder. Curr Opin Genet Dev. 2006;16:260-9.
  7. Basel-Vanagaite L. Genetics of autosomal recessive nonsyndromic mental retardation: recent advances. Clin Genet. 2007;72:167-74.
  8. Garshasbi M, Hadavi V, Habibi H, et al. A defect in the TuSC3 gene is associated with autosomal recessive mental retardation. Am J Hum Genet 2008;82: 1158-1164.
  9. Rafiq MA, Ansar M, Marshall CR, et al. Mapping of three novel loci for non- syndromic autosomal recessive mental retardation (NS-ARMR) in consanguineous families from Pakistan. Clin Genet. 2010; 78: 478-83.
  10. Molinari F, Rio M, Meskenaite V, et al. Truncating neurotrypsin mutation in autosomal recessive non syndromic mental retardation. Science 2002; 298: 1779-81.
  11. Didelot G, Molinari F, Tchenio P, et al. Tequila, a neurotrypsin ortholog, regulates long-term memory formation in Drosophila. Science 2006;313: 851-53.
  12. Mitsui S, Yamaguchi N, Osako Y, Yuri K. Enzymatic properties and localization of motopsin (PRSS12), a protease whose absence causes mental retardation. Brain Res 2007; 1136: 1-12.
  13. Higgins J, Rosen D, Loveless J, Clyman J, Grauy M. A gene for non syndromic mental retardation maps to chromosome 3p25- pter. Neurology 2000;55: 335-40.
  14. Higgins J, Pucilowska J, Lombardi R, Rooney J. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. Neurology 2004;63:1927-1931.
  15. Xin W, Xiahua N, Peilin C, Xin C, Yaqiong S, Qihan W. Primary function analysis of human mental retardation gene CRBN. Mol Bio Rep 2008;35: 251-6.
  16. Basel-Vanagaite L, Alkelai A, Straussberg R, et al. Mapping of a new locus for autosomal recessive non-syndromic mental retardation in the chromosomal region 19p13.12-p13.2: further genetic heterogeneity. J Med Genet 2003; 40:729-32.
  17. Basel-Vanagaite L, Attia R, Yahav M, et al. The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation. J Med Genet 2006; 43: 203-210.
  18. Ou XM, Lemonde S, Jafar-Nejad H, et al. Freud-1: a neuronal calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosci 2003: 23: 7415-7425
  19. Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 1999:89: 999-1002.
  20. Uyguner O, Kayserili H, Li Y, et al. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1- p13.3. Clin Genet 2007; 71:212-19.
  21. Motazacker MM, Rost BR, Hucho T, et al. A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. Am J Hum Genet. 2007; 81:792-8.
  22. Lerma J. Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 2003;4: 481-95
  23. Molinari F, Foulquier F, Tarpey PS, et al. Oligosaccharyltransferase subunit mutations in non syndromic mental retardation. Am J Hum Genet 2008;82: 1150-57.
  24. Mochida GH, Mahajnah M, Hill AD, et al. A truncating mutation of TRAPPC9 is associated with autosomal-recessive intellectual disability and postnatal microcephaly. Am J Hum Genet. 2009;85:897-902.
  25. Philippe O, Rio M, Carioux A, et al. Combination of linkage mapping and microarray-expression analysis identifies NFkappaB signaling defect as a cause of autosomal-recessive mental retardation. Am J Hum Genet. 2009; 85:903-8.
  26. Mir A, Kaufman L, Noor A, et al. Identification of mutations in TRAPPC9, which encodes the NIK- and IKK-beta-binding protein, in nonsyndromic autosomal-recessive mental retardation. Am J Hum Genet. 2009; 85:909-15.