High functioning fragile X males

Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression

R. J. Hagerman, C. E. Hull, J. F. Safanda, I. Carpenter, L. W. Staley, R. A. O'Connor, C. Seydel, M. M M Mazzocco, K. Snow, S. N. Thibodeau, D. Kuhl, D. L. Nelson, C. T. Caskey, A. K. Taylor

Research output: Contribution to journalArticle

Abstract

Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR-1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR-1 protein, albeit at lower levels than normal. FMR-1 protein was not present in retarded fra(X) males. Significant FMR-1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males.

Original languageEnglish (US)
Pages (from-to)298-308
Number of pages11
JournalAmerican Journal of Medical Genetics
Volume51
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Mutation
Proteins
DNA
Cytogenetics
Methylation
Research

Keywords

  • FMR-1 gene
  • fragile X syndrome
  • high functioning
  • Martin-Bell syndrome
  • methylation
  • mosaic

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Hagerman, R. J., Hull, C. E., Safanda, J. F., Carpenter, I., Staley, L. W., O'Connor, R. A., ... Taylor, A. K. (1994). High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. American Journal of Medical Genetics, 51(4), 298-308. https://doi.org/10.1002/ajmg.1320510404

High functioning fragile X males : Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. / Hagerman, R. J.; Hull, C. E.; Safanda, J. F.; Carpenter, I.; Staley, L. W.; O'Connor, R. A.; Seydel, C.; Mazzocco, M. M M; Snow, K.; Thibodeau, S. N.; Kuhl, D.; Nelson, D. L.; Caskey, C. T.; Taylor, A. K.

In: American Journal of Medical Genetics, Vol. 51, No. 4, 1994, p. 298-308.

Research output: Contribution to journalArticle

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', American Journal of Medical Genetics, vol. 51, no. 4, pp. 298-308. https://doi.org/10.1002/ajmg.1320510404
Hagerman, R. J. ; Hull, C. E. ; Safanda, J. F. ; Carpenter, I. ; Staley, L. W. ; O'Connor, R. A. ; Seydel, C. ; Mazzocco, M. M M ; Snow, K. ; Thibodeau, S. N. ; Kuhl, D. ; Nelson, D. L. ; Caskey, C. T. ; Taylor, A. K. / High functioning fragile X males : Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. In: American Journal of Medical Genetics. 1994 ; Vol. 51, No. 4. pp. 298-308.
@article{b3507b7e1b904633ac3c4d2618a05f5f,
title = "High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression",
abstract = "Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13{\%}) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR-1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR-1 protein, albeit at lower levels than normal. FMR-1 protein was not present in retarded fra(X) males. Significant FMR-1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males.",
keywords = "FMR-1 gene, fragile X syndrome, high functioning, Martin-Bell syndrome, methylation, mosaic",
author = "Hagerman, {R. J.} and Hull, {C. E.} and Safanda, {J. F.} and I. Carpenter and Staley, {L. W.} and O'Connor, {R. A.} and C. Seydel and Mazzocco, {M. M M} and K. Snow and Thibodeau, {S. N.} and D. Kuhl and Nelson, {D. L.} and Caskey, {C. T.} and Taylor, {A. K.}",
year = "1994",
doi = "10.1002/ajmg.1320510404",
language = "English (US)",
volume = "51",
pages = "298--308",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - High functioning fragile X males

T2 - Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression

AU - Hagerman, R. J.

AU - Hull, C. E.

AU - Safanda, J. F.

AU - Carpenter, I.

AU - Staley, L. W.

AU - O'Connor, R. A.

AU - Seydel, C.

AU - Mazzocco, M. M M

AU - Snow, K.

AU - Thibodeau, S. N.

AU - Kuhl, D.

AU - Nelson, D. L.

AU - Caskey, C. T.

AU - Taylor, A. K.

PY - 1994

Y1 - 1994

N2 - Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR-1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR-1 protein, albeit at lower levels than normal. FMR-1 protein was not present in retarded fra(X) males. Significant FMR-1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males.

AB - Fragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR-1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR-1 protein, albeit at lower levels than normal. FMR-1 protein was not present in retarded fra(X) males. Significant FMR-1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males.

KW - FMR-1 gene

KW - fragile X syndrome

KW - high functioning

KW - Martin-Bell syndrome

KW - methylation

KW - mosaic

UR - http://www.scopus.com/inward/record.url?scp=0028264043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028264043&partnerID=8YFLogxK

U2 - 10.1002/ajmg.1320510404

DO - 10.1002/ajmg.1320510404

M3 - Article

VL - 51

SP - 298

EP - 308

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 4

ER -