Combined cytogenetic and molecular analyses for the diagnosis of Prader-Willi/Angelman syndromes.
Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that result from the loss of expression of imprinted genes in the paternal (PWS) or maternal (AS) 15q11-q13 chromosome. Diagnosis on a clinical basis is difficult in newborns and young infants; thus, a suitable molecular test capable of revealing chromosomal abnormalities is required. We used a variety of cytogenetic and molecular approaches, such as, chromosome G banding, fluorescent in situ hybridization, a DNA methylation test, and a set of chromosome 15 DNA polymorphisms to characterize a cohort of 27 PWS patients and 24 suspected AS patients. Molecular analysis enabled the reliable diagnosis of 14 PWS and 7 AS patients, and their classification into four groups: (A) 6 of these 14 PWS subjects (44 %) had deletions of paternal 15q11-q13; (B) 4 of the 7 AS patients had deletions of maternal 15q11-q13; (C) one PWS patient (8 %) had a maternal uniparental disomy (UPD) of chromosome 15; (D) the remaining reliably diagnoses of 7 PWS and 3 AS cases showed abnormal methylation patterns of 15q11-q13 chromosome, but none of the alterations shown by the above groups, although they may have harbored deletions undetected by the markers used. This study highlights the importance of using a combination of cytogenetic and molecular tests for a reliable diagnosis of PWS or AS, and for the identification of genetic alterations.
Borelina
Daniel
D
Genetica y Biologia Molecular, Facultad de Farmacia y Bioquimica, UBA, Buenos Aires, Argentina.
Engel
Nora
N
Esperante
Sebastian
S
Ferreiro
Veronica
V
Ferrer
Marcela
M
Torrado
Maria
M
Goldschmidt
Ernesto
E
Francipane
Liliana
L
Szijan
Irene
I
D000293:Adolescent; D017204:Angelman Syndrome / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics