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Cognitive ability predicts degree of genetic abnormality in participants with 18q deletions

Published online by Cambridge University Press:  26 August 2005

MARGARET SEMRUD-CLIKEMAN
Affiliation:
Department of Educational Psychology, University of Texas at Austin, University Station, Austin, Texas
NORA M. THOMPSON
Affiliation:
Disabled Student Services, University of Washington, Seattle, Washington
BECKY L. SCHAUB
Affiliation:
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
ROBIN LEACH
Affiliation:
Department of Cellular and Molecular Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
ANDREA HESTER
Affiliation:
Department of Educational Psychology, University of Texas at Austin, University Station, Austin, Texas
DANIEL E. HALE
Affiliation:
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
AND JANNINE D. CODY
Affiliation:
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Abstract

One of the most common chromosomal deletions is a loss of genetic material from the long arm of chromosome 18. Most individuals with this condition exhibit mental retardation (68%), yet previous attempts to link cognitive status to deletion size have not shown an association, possibly because cases with additional genetic abnormalities were included. We studied 46 participants ranging from 3 to 35 years of age who had a pure genetic abnormality by excluding those with mosaicism or complex genetic rearrangements. Our patients had terminal deletions ranging from a proximal breakpoint at 18q21.1 (greater genetic abnormality, larger deletion size) to a more distal breakpoint at 18q23 characterized with molecular genetic techniques. Cognitive ability, assessed with the age-appropriate measure (Bayley, 1993, Differential Ability Scale, Wechsler Scales), ranged from IQ = 49 to 113, with a predominance of mild and moderate mental retardation. Using multivariate regression, deletion size breakpoint rank order was predicted by cognitive ability, age, and adaptive behavior (Vineland Adaptive Behavior Scales), accounting for 36% of the variance in deletion size. However, lower cognitive ability (beta = .34, p = .032) and younger age (beta = .296, p = .024) predicted a larger deletion size, but adaptive behavior (beta = .225, p = .15) did not. An additional multivariate regression showed that cognitive ability and age together accounted for 33% of the variance in deletion size, whereas univariate regression showed that cognitive ability accounted for 26% of the variance and age accounted for 11% of the variance. These findings suggest that degree of cognitive impairment is associated with genetic abnormality when a large sample of individuals with “pure” deletions of genetic material from chromosome 18 is examined. (JINS, 2005, 11, 584–590.)

Type
Research Article
Copyright
© 2005 The International Neuropsychological Society

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References

REFERENCES

Bayley, N. (1993). Bayley Scales of Infant Development 2nd Edition. San Antonio, TX: Psychological Corporation.
Brkanac, Z., Cody, J.D., Leach, R.J., & DuPont, B.R. (1998). Identification of cryptic rearrangements in patients with the 18q- deletion syndrome. American Journal of Human Genetics, 62, 15001506.CrossRefGoogle Scholar
Cody, J.D., Brkanac, Z., Pierce, J.F., Plaetke, R., Ghidoni, P.D., Kaye, C.I., & Leach, R.J. (1997). Preferential loss of the paternal alleles in the 18q- syndrome. American Journal of Medical Genetics, 69, 280286.3.0.CO;2-N>CrossRefGoogle Scholar
Cody, J.D., Ghidoni, P.D., DuPont, B.R., Hale, D.E., Hilsenbeck, S.G., Stratton, R.F., Hoffman, D.S., Muller, S., Schaub, R.L., Leach, R.J., & Kaye, C.I. (1999). Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q. American Journal of Medical Genetics, 85, 455462.3.0.CO;2-Z>CrossRefGoogle Scholar
Crowe, T.K., Deitz, J.C., & Bennett, F.C. (1987). The relationship between the Bayley Scales of Infant Development and preschool gross motor and cognitive performance. The American Journal of Occupational Therapy, 41, 374378.CrossRefGoogle Scholar
Elliott, C. (1990). Differential Abilities Scale. San Antonio, TX: Psychological Corporation.
Farrar, D.C. & Harbor, L.A. (1989). Responses to a learning task at 6 months and I.Q. test performance during the preschool years. International Journal of Behavioral Development, 12, 101114.Google Scholar
Gay, C.T., Hardies, L.J., Rauch, R.A., Lancaster, J.L., Plaetke, R., DuPont, B.R., Cody, J.D., Cornell, J.E., Herndon, R.C., Ghidoni, P.D., Schiff, J.M., Kaye, C.I., Leach, R.J., & Fox, P.T. (1997). Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: Evidence for myelin basic protein haploinsufficiency. American Journal of Medical Genetics, 74, 422431.3.0.CO;2-K>CrossRefGoogle Scholar
Ghidoni, P.D., Hale, D.E., Cody, J.D., Gay, C.T., Thompson, N.M., McClure, E.B., Danney, M.M., Leach, R.J., & Kaye, C.I. (1997). Growth hormone insufficiency associated in the 18q- deletion syndrome. American Journal of Medical Genetics, 69, 712.3.0.CO;2-P>CrossRefGoogle Scholar
Hale, D.E., Cody, J.D., Baillargeon, J., Schaub, R., Danney, M.M., & Leach, R.J. (2000). The spectrum of growth abnormalities in children with 18q deletions. Journal of Clinical Endocrinology Metabolism, 85, 44504454.Google Scholar
Kline, A.D., White, M.E., Wapner, R., Rojas, K., Biesecker, L.G., Kamholz, J., Zackai, E.H., Muenke, M., Scott, C.I., Jr., & Overhauser, J. (1993). Molecular analysis of the 18q- syndrome—and correlation with phenotype. American Journal of Human Genetics, 52, 895906.Google Scholar
Kochunov, P., Lancaster, J., Hardies, J., Thompson, P.M., Woods, R.P., Cody, J.D., Hale, D.E., Laird, A., & Fox, P.T. (2005). Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization. Human Brain Mapping, 24, 325331.CrossRefGoogle Scholar
Mahr, R.N., Moberg, P.J., Overhauser, J., Strathdee, G., Kamholz, J., Loevner, L.A., Campbell, H., Zackai, E.H., Reber, M.E., Mozley, D.P., Brown, L., Turetsky, B.I., & Shapiro, R.M. (1996). Neuropsychiatry of 18q- syndrome. American Journal of Medical Genetics, 67, 172178.3.0.CO;2-U>CrossRefGoogle Scholar
Miller, G., Mowrey, P.N., Hopper, K.D., Frankel, C.A., & Ladda, R.L. (1990). Neurologic manifestations in 18q- syndrome. American Journal of Human Genetics, 37, 128132.CrossRefGoogle Scholar
Sattler, J. (2002). Assessment of children: Cognitive applications (4th ed.). San Diego, CA: JM Sattler.
Schnizel, A. (1984). 18q- syndrome. In Catalogue of unbalanced chromosome aberrations in man (pp. 611613). New York: Walter deGruyter.
Sparrow, S.S., Balla, D.A., & Cicchetti, D.V. (1984). Vineland Adaptive Behavior Scales. Circle Pines, MN: American Guidance Service.
Strathdee, G., Zackai, E.H., Shapiro, R., Kamholz, J., & Overhauser, J. (1996). Analysis of clinical variations seen in patients with 18q terminal deletions. American Journal of Medical Genetics, 59, 476483.Google Scholar
Wechsler, D. (1981). Manual for the Wechsler Intelligence Scale for Children–Revised. San Antonio, TX: Psychological Corporation.
Wechsler, D. (1997). Manual for the Wechsler Adult Intelligence Scale III. San Antonio, TX: Psychological Corporation.
Wechsler, D. (2000). Manual for the Wechsler Preschool and Primary Scales of Intelligence III. San Antonio, TX: Psychological Corporation.