Journal of the International Neuropsychological Society



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


MARGARET  SEMRUD-CLIKEMAN  a1 c1 , NORA M.  THOMPSON  a2 , BECKY L.  SCHAUB  a3 , ROBIN  LEACH  a4 , ANDREA  HESTER  a1 , DANIEL E.  HALE  a5 and AND JANNINE D.  CODY  a5
a1 Department of Educational Psychology, University of Texas at Austin, University Station, Austin, Texas
a2 Disabled Student Services, University of Washington, Seattle, Washington
a3 Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
a4 Department of Cellular and Molecular Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
a5 Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Article author query
semrud-clikeman m   [PubMed][Google Scholar] 
thompson nm   [PubMed][Google Scholar] 
schaub bl   [PubMed][Google Scholar] 
leach r   [PubMed][Google Scholar] 
hester a   [PubMed][Google Scholar] 
hale de   [PubMed][Google Scholar] 
cody ajd   [PubMed][Google Scholar] 

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.)

(Received April 8 2004)
(Revised April 7 2005)
(Accepted April 18 2005)


Key Words: Mental retardation; Chromosomal deletion; Phenotype; Breakpoint; Rank order; Nonverbal ability.

Correspondence:
c1 Reprint requests to: Margaret Semrud-Clikeman Ph.D., Department of Educational Psychology, D5800, 1 University Station, Austin, TX 78712. E-mail: peg.semrud@mail.utexas.edu


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