Genotype does not predict severity of behavioural phenotype in juvenile neuronal ceroid lipofuscinosis (Batten disease).
OBJECTIVE
The primary aim of this investigation was to examine genotype and clinical phenotype differences in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL) who were homozygous for a common disease-causing deletion or compound heterozygous. The secondary aim was to cross-validate the Child Behavior Checklist (CBCL) and the Unified Batten Disease Rating Scale (UBDRS), a disease-specific JNCL rating scale.


METHODS
Sixty individuals (28 males, 32 females; mean age 15y 1mo, SD 4y 9mo, range 5y 8mo--31y 1mo) with JNCL completed the UBDRS.


RESULTS
No significant genotype and clinical phenotype differences were identified when comparing individuals homozygous for the deletion with a heterogeneous group of compound heterozygous individuals. There were significant correlations among related behaviour items and scales on the CBCL and UBDRS (Spearman's rho ranging from 0.39 [p<0.05] to 0.72 [p<0.01]). Behaviour and physical function ratings were uncorrelated, supporting divergent validity of these two constructs in JNCL.


CONCLUSIONS
Previous reports of genotype and clinical phenotype differences were unsupported in this investigation, which did not find differences between individuals homozygous or heterozygous for the CLN3 deletion. The CBCL, an already validated measure of behaviour problems, appears valid for use in JNCL and cross-validates well with the UBDRS.
Adams
Heather R
HR
Division of Child Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. heather_adams@urmc.rochester.edu
Beck
Christopher A
CA
Levy
Erika
E
Jordan
Rachel
R
Kwon
Jennifer M
JM
Marshall
Frederick J
FJ
Vierhile
Amy
A
Augustine
Erika F
EF
de Blieck
Elisabeth A
EA
Pearce
David A
DA
Mink
Jonathan W
JW
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D017384:Sequence Deletion; D012720:Severity of Illness Index; D055815:Young Adult
C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones