Tissue heterogeneity of the FMR1 mutation in a high-functioning male with fragile X syndrome

American Journal of Medical Genetics

Volumn 84, Issue 3, 1999, Pages 233-239

  Taylor, Annette K ^a   Tassone, Flora ^a,d   Dyer, Pamela N ^a   Hersch, Steven M ^b   Harris, Jennifer B ^c   Greenough, William T ^c   Hagerman, Randi J ^d,e  

^a Kimball Genetics Inc   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^d CHILDREN S HOSPITAL   (United States)

^e UNIVERSITY OF COLORADO   (United States)

Author keywords

Autopsy; FMR1 mutation; Fragile X syndrome; High functioning; Methylation; Postmortem; Tissue heterogeneity; Trinucleotide repeat instability; Unmethylated full mutation

Indexed keywords

ARTICLE; BRAIN REGION; CASE REPORT; CELL HETEROGENEITY; CHROMOSOME MUTATION; CONTROLLED STUDY; FRAGILE X SYNDROME; HUMAN; IMMUNOCYTOCHEMISTRY; MALE; METHYLATION; PARIETAL LOBE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SOUTHERN BLOTTING; TRINUCLEOTIDE REPEAT;

AGED; BRAIN; DENDRITES; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MUTATION; NERVE TISSUE PROTEINS; RNA-BINDING PROTEINS; TISSUE DISTRIBUTION;

EID: 0033612337     PISSN: 01487299     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1096-8628(19990528)84:3<233::AID-AJMG14>3.0.CO;2-6     Document Type: Article

References (40)

1. Brown WT, Houck GE, Jeziorowska A, Levinson FN, Ding X, Dobkin C, Zhong N, Henderson J, Brooks SS, Jenkins EC. 1993. Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. JAMA 270:1569-1575.
2. Chen X, Mariappan SVS, Catasti P, Ratliff R, Moyzis RK, Laayoun A, Smith SS, Bradbury EM, Gupta G. 1995. Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications. Proc Natl Acad Sci USA 92:5199-5203.
3. Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, Greenough WT. 1997. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci USA 94: 5401-5404.
4. de Graaff E, Willemsen R, Zhong N, de Die-Smulders CEM, Brown WT, Freling G, Oostra B. 1995. Instability of the CGG repeat and expression of the FMR1 protein in a male fragile X patient with a lung tumor. Am J Hum Genet 57:609-618.
5. de Vries BBA, Jansen CCAM, Duits AA, Verheij C, Willemsen R, van Hemel JO, van den Ouweland AMW, Niermeijer MF, Oostra BA, Halley DJJ. 1996. Variable FMR1 gene methylation of large expansions leads to variable phenotype in three males from one fragile X family. J Med Genet 33:1007-1010.
6. Devys D, Biancalana V, Rousseau F, Boué J, Mandel J-L, Oberlé I. 1992. Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development. Am J Med Genet 43:208-216.
7. Devys D, Lutz Y, Rouyer N, Bellocq J-P, Mandel J-L. 1993. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 4:335-340.
8. Dobkin CS, Nolin SL, Cohen I, Sudhalter V, Bialer MG, Ding X-H, Jenkins EC, Zhong N, Brown WT. 1996. Tissue differences in fragile X mosaics: mosaicism in blood cells may differ greatly from skin. Am J Med Genet 64:296-301.
9. Feng Y, Gutekrunst C-A, Eberhart D, Yi H, Warren ST, Hersch SM. 1997. Fragile X mental retardation protein:nucleocytoplasmic shuttling and association with ribosomes. J Neurosci 17:1539-1547.
10. Feng Y, Zhang F, Lokey LK, Chastain JL, Lakkis L, Eberhart D, Warren ST. 1995. Translational suppression by trinucleotide repeat expansion at FMR1. Science 268:731-734.
11. Hagerman RJ, Hull CE, Safanda JF, Carpenter I, Staley LW, O'Connor RA, Seydel C, Mazzocco MMM, Snow K, Thibodeau SN, Kuhl D, Nelson DL, Caskey CT, Taylor AK. 1994. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet 51:298-308.
12. Hinton VJ, Brown WT, Wisniewski K, Rudelli RD. 1991. Analysis of neo-cortex in three males with the fragile X syndrome. Am J Med Genet 41:289-294.
13. Kambouris M, Snow K, Thibodeau S, Bluhm D, Green M, Feldman GL. 1996. Segregation of the fragile X mutation from a male with a full mutation: unusual somatic instability in the FMR-1 locus. Am J Med Genet 64:404-407.
14. Lachiewicz AM, Spiridigliozzi GA, McConkie-Rosell A, Burgess D, Feng Y, Warren ST, Tarleton J. 1996. A fragile X male with a broad smear on Southern blot analysis representing 100-500 CGG repeats and no methylation at the EagI site of the FMR-1 gene. Am J Med Genet 64:278-282.
15. Loesch DZ, Huggins R, Hay DA, Gedeon AK, Mulley JC, Sutherland GR. 1993. Genotype-phenotype relationships in fragile X syndrome: a family study. Am J Hum Genet 53:1064-1073.
16. Maddalena A, Yadvish KN, Spence WC, Howard-Peebles PN. 1996. A fragile X mosaic male with a cryptic full mutation detected in epithelium but not in blood. Am J Med Genet 64:309-312.
17. Malter HE, Iber JC, Willemsen R, de Graaff E, Tarleton JC, Leisti J, Warren ST, Oostra BA. 1997. Characterization of the full fragile X syndrome mutation in fetal gametes. Nat Genet 15:165-169.
18. McConkie-Rosell A, Lachiewicz AM, Spiridigliozzi GA, Tarleton J, Scheonwald S, Phelan CM, Goonewardena P, Ding X, Brown WT. 1993. Evidence that methylation of the FMR-1 locus is responsible for variable phenotypic expression of the fragile X syndrome. Am J Hum Genet 53:800-809.
19. McMurray CT. 1995. Mechanisms of DNA expansion. Chromosoma (Berl) 104:2-13.
20. Merenstein SA, Shyu V, Sobesky WE, Staley L, Berry-Kravis E, Nelson DL, Lugenbeel KA, Taylor AK, Pennington BF, Hagerman RJ. 1994. Fragile X syndrome in a normal IQ male with learning and emotional problems. J Am Acad Child Adolesc Psychiatry 33:1316-1321.
21. Moutou C, Vincent M-C, Biancalana V, Mandel J-L. 1997. Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic. Hum Mol Genet 6:971-979.
22. Nolin SL, Houck GE Jr., Blumstein H, Ye LL, Dobkin CS, Brown WT. 1997. Single cell analysis shows different FMR1 CGG repeat stability in sperm and lymphocytes of premutation males. Am J Hum Genet 61(Supp]):A316.
23. Nolin SL, Lewis FA, Ye LL, Houck GE Jr., Glicksman AE, Limprasert P, Li SY, Zhong N, Ashley AE, Feingold E, Sherman SL, Brown WT. 1996. Familial transmission of the FMR1 CGG repeat. Am J Hum Genet 59:1252-1261.
24. Oberlé I, Rousseau F, Heitz D, Kretz C, Devys D, Hanauer A, Boué J, Bertheas MF, Mandel J-L. 1991. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1097-1102.
25. Reyniers E, Martin J-J, Cras P, Van Marck E, Handig I, Jorens HZJ, Oostra BA, Kooy RF, Willems PJ. 1999. Postmortem examination of two fragile X brothers with an FMR1 full mutation. Am J Med Genet 84:000-000.
26. Reyniers E, Vits L, de Boulle K, Van Roy B, Van Velzen D, de Graaff E, Verkerk AJMH, Jorens HZJ, Darby JK, Oostra BA, Willems PJ. 1993. The full mutation in the FMR1 gene of male fragile X patients is absent in their sperm. Nat Genet 4:143-146.
27. Rousseau F, Robb LJ, Rouillard P, der Kaloustian VM. 1994. No mental retardation in a man with 40% abnormal methylation at the FMR-1 locus and transmission of sperm cell mutations as premutations. Hum Mol Genet 3:927-930
28. Rudelli RD, Brown WT, Wisniewski K, Jenkins EC, Laure-Kamionowska M, Connell F, Wisniewski HM. 1985. Adult fragile X syndrome clinical neuropathologic findings. Acta Neuropathol 67:289-295.
29. Smeets HJM, Smits APT, Verheij CE, Theelen JPG, Willemsen R, van de Burgt I, Hoogeveen AT, Oosterwijk JC, Oostra BA. 1995. Normal phenotype in two brothers with a full FMR1 mutation. Hum Mol Genet 4:2103-2108.
30. Steyaert J, Borghgraef M, Legius E, Fryns J-P. 1996. Molecular intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene. Am J Med Genet 64:274-277.
31. Sutherland GR, Gedeon A, Kornman L, Donnelly A, Byard RW, Mulley JC, Kremer E, Lynch M, Pritchard M, Yu S, Richards RI. 1991. Prenatal diagnosis of fragile X syndrome by direct detection of the unstable DNA sequence. N Engl J Med 325:1720-1722.
32. Tassone F, Hagerman RJ, Gane LW, Taylor AK. 1999a. Strong similarities of the FMR1 mutation in multiple tissues: postmortem studies of a male with a full mutation and a male carrier of a premutation. Am J Med Genet 84:240-244.
33. Tassone F, Hagerman RJ, Iklé D, Dyer PN, Lampe M, Willemsen R, Oostra BA, Taylor AK. 1999b. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet 84:250-261.
34. Taylor AK, Safanda JF, Fall MZ, Quince C, Lang KA, Hull CE, Carpenter I, Staley LW, Hagerman RJ. 1994a. Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA 271:507-514.
35. Taylor AK, Safanda JF, Lugenbeel KA, Nelson DL, Hagerman RJ. 1994b. Molecular and phenotypic studies of fragile X males with variant methylation of the FMR1 gene reveal that the degree of methylation influences clinical severity. Am J Hum Genet 55(Suppl):A18.
36. Wang Z, Taylor AK, Bridge JA. 1996. FMR1 fully expanded mutation with minimal methylation in a high functioning fragile X male. J Med Genet 33:376-378.
37. Wöhrle D, Hennig I, Vogel W, Steinbach P. 1993. Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat Genet 4:140-142.
38. Wöhrle D, Hirst MC, Kennerknecht I, Davies KE, Steinbach P. 1992. Genotype mosaicism in fragile X fetal tissues. Hum Genet 89:114-116.
39. Wöhrle D, Salat U, Gläser D, Mücke J, Meisel-Stosiek M, Schindler D, Vogel W, Steinbach P. 1998. Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats. J Med Genet 35:103-111.
40. Wöhrle D, Schwemmle S, Steinbach P. 1996. DNA methylation and triplet repeat stability. Am J Med Genet 64:266-267.