Molecular study of the Prader-Willi syndrome: deletion, RFLP, and phenotype analyses of 50 patients

• Published in: American journal of medical genetics Vol. 41; no. 1; p. 54
• Main Authors: Hamabe, J, Fukushima, Y, Harada, N, Abe, K, Matsuo, N, Nagai, T, Yoshioka, A, Tonoki, H, Tsukino, R, Niikawa, N
• Format: Journal Article
• Language: English
• Published: United States 01.10.1991
• Subjects: Adolescent; Adult; Blotting, Southern; Child; Child, Preschool; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 15; DNA Mutational Analysis; Female; Humans; Infant; Male; Phenotype; Polymorphism, Restriction Fragment Length; Prader-Willi Syndrome - genetics; Translocation, Genetic - genetics
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320410116

Deletion and RFLP studies with 5 cloned DNA markers localized at 15q11.2 were performed in 50 patients with the Prader-Willi syndrome (PWS). A one-copy density (deletion) for at least one of 4 loci, D15S9, D15S11, D15S10, D15S12, was detected in 32 (64%) of the 50 patients; deletions of each of the 4 loci were found in 29, 30, 29, and 28 patients, respectively. Three patients showed 4 or more copy density for D15S12 locus, in addition to deletions. The remaining 18 patients showed two-copy densities for each of the 4 loci. A common site of rearrangements among our 32 patients as well as the reported patients seemed to be confined to a segment between D15S9 and D15S11, suggesting the putative PWS gene locus in this segment. Of 6 patients who have cytologic deletions but did not show any molecular deletions, 3 have normal size of hands and feet, and 4 have normally pigmented skin and hair. The normal pigmentation was also observed in 3 patients who had small molecular deletions in the examined 5-locus segment. These observations may support the conception of contiguous gene syndrome. RFLP analysis demonstrated maternal uniparental isodisomy of chromosomes 15 in both a patient with 45,t(15q;15q) and a karyotypically normal patient. Based on the results of the present study, a new model is proposed to explain the occurrence of PWS with a variety of chromosome abnormalities, including partial monosomy, disomy, trisomy, and/or tetrasomy for 15q11.2. The normal development may require an even or more "number ratio" of paternally derived allele(s) to maternally derived allele(s) of the gene(s) localized at 15q11.2, and a disturbance of the ratio would lead to the PWS phenotype.