Relationship between molecular, cytogenetic and clinical parameters in 63 individuals with full mutation in FMR1 gene

• Autorzy: Milewski M , Bal J , Bocian E , Obersztyn E , Mazurczak T
• Języki publikacji: EN

Abstrakty

EN

Relationship between selected molecular, cytogenetic and clinical parameters was analysed in a group of 63 individuals (45 males and 18 females) with full fragile X mutation. Significant correlation between the size and somatic instability of fully mutated alleles in both males and females was found. Possible explanations of this result are discussed. With respect to the mutation size, an apparent difference was observed between males with different degree of mental retardation. No such difference appeared when affected and normal females with full mutation were compared. The proportion of mutated active X chromosome was significantly higher in mentally retarded females than in those without any mental impairment.

Słowa kluczowe

EN

inactivation; human disease; gene; X chromosome; mental retardation; clinical parameter; mental status; full mutation; cytogenetic parameter; molecular parameter; fragile X syndrome; amplification size

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 1996
• Tom: 37
• Numer: 2
• Opis fizyczny: p.205-215,fig.

Twórcy

autor

Milewski M

• Department of Genetics, National Research Institute of Mother and Child, ul.Kasprzaka 17a, 01-211 Warszawa, Poland

autor

Bal J

• Department of Genetics, National Research Institute of Mother and Child, ul.Kasprzaka 17a, 01-211 Warszawa, Poland

autor

Bocian E

• Department of Genetics, National Research Institute of Mother and Child, ul.Kasprzaka 17a, 01-211 Warszawa, Poland

autor

Obersztyn E

• Department of Genetics, National Research Institute of Mother and Child, ul.Kasprzaka 17a, 01-211 Warszawa, Poland

autor

Mazurczak T

• Department of Genetics, National Research Institute of Mother and Child, ul.Kasprzaka 17a, 01-211 Warszawa, Poland

Bibliografia

• ABRAMS M.T., REISS A.L., FREUND L.S., BAUMGARDNER T.L., CHASE G.A., DENCKLA M.B. (1994). Molecular-neurobehavioral associations in females with the fragile X full mutation. Am. J. Med. Genet. 51: 317-327.
• DEVYS O., BIANCALANA V., ROUSSEAU F., BOUÉ J., MANDEL J.L., OBERLÉ I. (1992). Analysis of full 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.
• FU Y.H., KUHL D.P.A., PIZZUN A., PIERETTI M., SUTCLIFFE J.S., RICHARDS S., VERKERK A.J.M.H., HOLDEN J J.A., FENWICK JR M.G., WARREN S.T., OOSTRA B.A., NELSON D.L., CASKEY C.T. (1991). Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67: 1047-1058.
• JACKY P.B., AHUJA Y.R., ANYANE-YEBOA K., BREG W.R., CARPENTER N.J., FROSTER- ISKENIUS U.G., FRYNS J.P., GLOVER T.W., GUSTAVSON K.H., HOEGERMAN S.F., HOLMGREN G., HOWARD-PEEBLES P.N., JENKINS E.C., KRAWCZUN M.S., NERI G., PETTIGREW A., SCHAAP T., SCHORNBERG S.A., SHAPIRO L.R, SPINNER N., STEINBACH P., VIANNA-MORGANTE A.M., WATSON M.S., WILMOT P.L. (1991). Guidelines for the preparation and analysis of the fragile X chromosome in lymphocytes. Am. J. Med. Genet. 38: 400-403.
• KOLEHMAINEN K., KARANT Y. (1994). Modeling methylation and IQ scores in fragile X females and mosaic males. Am. J. Med. Genet. 51: 328-338.
• KREMER E.J., PRITCHARD M., LYNCH M., YU S., HOLMAN K., BAKERE., WARREN S.T., SCHLESSINGER D., SUTHERLAND G.R., RICHARDS R.I. (1991). Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252: 1711-1714.
• LOESCH D.Z., HUGGINS R., HAY D.A., GEDEON A.K., MULLEY J.C., SUTHERLAND G.R. (1993). Genotype-phenotype relationships in fragile X syndrome: A family study. Am. J. Hum. Genet. 53: 1064-1073.
• McCONKIE-ROSELL A., LACHIEWICZ A.M., SPIRIDIGLIOZZI G.A., TARLETON J., SCHOENWALD S., PHELAN M.C., GOONEWARDENA P., DING X., BROWN W.T. (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.
• MILLER S.A., DYKES D.D., POLESKY H.F. (1988). A simple salting procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 17: 1784.
• OBERLÉ I., ROUSSEAU F., HEITZ D., KRETZ C., DEVYS D., HANAUER A., BOUÉ J., BERTHEAS M.F., MANDEL J.L. (1991). Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1179-1181
• PIERETTI M., ZHANG F., FU Y.H., WARREN S.T., OOSTRA B.A., CASKEY C.T., NELSON D.L. (1991). Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66: 817-822.
• RICHARDS R., SUTHERLAND G.R. (1992). Dynamic mutations: a new class of mutations causing human disease. Cell 70: 709-712.
• ROUSSEAU F., HEITZ D., OBERLÉ I., MANDEL J.L. (1991a). Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation. J. Med. Genet. 28: 830-836.
• ROUSSEAU F., HEITZ D., BIANCALANA V., BLUMENFELD S., KRETZ C., BOUÉ J., TOMMERUP N., van der HAGEN C., de LOZIER-BLANCHET C., CROQUETTE M.F., GILGENKRANTZ S., JALBERT P., VOELCKEL M.A., OBERLÉ I., MANDEL J.L. (1991b). Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N. Engl. J. Med. 325: 1673-1681.
• ROUSSEAU F., HEITZ O., TARLETON J., MacPHERSON J., MALMGREN H., DAHL N., BARNICOAT A., MATHEW C., MORNET E., TEJADA I., MADDALENA A., SPIEGEL R., SCHINZEL A., MARCOS J.A.G., SCHORDERAT D.F., SCHAAP T., MACCIONI L, RUSSO S., JACOBS P.A., SCHWARTZ C., MANDEL J.L. (1994). A multiccnter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB 12.3: The first 2,253 cases. Am. J. Hum. Genet. 55: 225-237.
• STALEY L.W., HULL C.E., MAZOCCO M.M.M., THIBODEAU S.N., SNOW K., WILSON V.L., TAYLOR A., McGAVRAN L., WEINER D., RIDDLE J., O'CONNOR R., HAGERMAN R.J. (1993). Molecular-clinical correlations in children and adults with fragile X syndrome. Am. J. Dis. Child. 147: 723-726.
• SUTCLIFFE J.S., NELSON D.L., ZHANG F., PIERETTI M., CASKEY C.T., SAXE D., WARREN S.T. (1992). DNA mcthylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1: 397-400.
• TAYLOR A.K., SAFANDA J.F., FALL M.Z., QUINCE C., LANG K.A., HULL C.E., CARPENTER I., STALEY L.W., HAGERMAN R.J. (1994). Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA 7: 507-514.
• VERKERK A.J.M.H., PIERETTI M., SUTCLIFFE J.S., FU Y.H., KUHL D.P.A., PIZZUTI A., REINER O., RICHARDS S., VICTORIA M.F., ZHANG F., EUSSEN B.E., OMMEN VAN G.J.B., BLONDEN L.A.J., RIGGINS G.J., CHASTAIN J.L., KUNST C.B., GAIJAARD H., CASKEY C.T., NELSON D.L., OOSTRA B.A., WARREN S.T. (1991). Identification of the gene (FMR-1) containing CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905-914.
• VRIES DE B.B.A., WIEGERS A.M., GRAAF DE E., VERKERK A.J.M.H., HEMEL VAN J.O., HALLEY DJ J., FRYNS J.P., CURFS L.M.G., NIERMEIJER M.F., OOSTRA B.A. (1993). Mental status and fragile X expression in relation to FMR-1 gene mutation. Eur. J. Hum. Genet. 1: 72-79.
• WÖHRLE D., HIRST M.C., KENNERKNECHT I., DAVIES K.E., STEINBACH P. (1992). Genotype mosaicism in fragile X tissue. Hum. Genet. 89: 114-116.