Clinical correlates of chromosome 15 deletions and maternal disomy in Prader-Willi syndrome
L. W. Lai, R. P. Erickson and S. B. Cassidy
Steele Memorial Children's Research Center, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson.
We conducted restriction fragment length polymorphism and methylation
pattern analyses on 26 typical and atypical patients with Prader-Willi
syndrome who did not have a cytogenetically detectable 15q11-13 deletion
and on four patients who did have this deletion and were clinically
atypical. Maternal disomy for chromosome 15 was identified in 12 patients
and paternal deletions in 15q11-13 were found in three cases. Patients with
chromosome 15 abnormalities had typical or near typical presentations,
based on published diagnostic criteria. Most of the absent criteria in this
group were age-dependent features. The remaining 15 patients, including
four previously thought to have a cytogenetically apparent 15q11-13
deletion, had neither chromosome 15 molecular abnormality, and these
patients were atypical. Patients with maternal disomy had advanced maternal
age, suggesting that nondisjunction is part of the etiology of uniparental
disomy. This study suggests that molecular diagnosis is critical in
patients with Prader-Willi syndrome who appear clinically atypical or who
lack a cytogenetically detectable 15q deletion. Methylation pattern
analysis is a useful adjunct diagnostic tool for Prader-Willi syndrome.
