Molecular and clinical study of 61 Angelman syndrome patients

✍ Scribed by Saitoh, Shinji ;Harada, Naoki ;Jinno, Yoshihiro ;Hashimoto, Katsuyo ;Imaizumi, Kiyoshi ;Kuroki, Yoshikazu ;Fukushima, Yohimitsu ;Sugimoto, Tateo ;Renedo, Mónica ;Wagstaff, Joseph ;Lalande, Marc ;Mutirangura, Apiwat ;Kuwano, Akira ;Ledbetter, David H. ;Niikawa, Norio

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 632 KB
• Volume: 52
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320520207

✦ Synopsis

We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15SIO and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (qllq131, showed no molecular deletion. Most clinical manifestations, including neu-