Prader‐Willi syndrome: Abstracts of a conference

The 15 papers presented at the Eleventh Annual Prader-Willi Syndrome Scientific Day ranged from those that explored the genetic origins of Prader-Willi syndrome (PWS) and prenatal molecular cytogenetic diagnosis to the measurement and treatment of medical, behavioral, and nutrition/exercise problems of affected children and adults. Several important findings emerged. First, there was more information describing imprinting mutations, a new genetic mechanism in Prader-Willi and Angelman syndromes. Further, there was the delineation of an imprinting center (IC) that controls the resetting of the imprinting during gametogenesis. At the same time, a description of a relaxation of imprinting in two patients with PWS was described (Rogan, Abstr. 2). Along these same lines, a survey of the age of diagnosis as a function of genetic status was reported by Gunay-Aygun et al. (Abstr. 5). Improved laboratory methods with a clearer specification of the most informative microsatellite markers for diagnosing uniparental disomy were reported by Christian et al. (Abstr. 3). This same group reported the use of methylation analysis specifically for SNRPN as a prenatal diagnostic tool in either abnormal lymphoblast cell lines (LB), cultured amniotic fluid, or chorionic villus samples. Endocrine abnormalities affecting males and females were reported by several researchers (Angulo, et al. Abstr. 7; Hanchett et al., Abstr. 9), and new findings regarding bone age were reported (Whitman and Myers, Abstr. 11). Methods for describing, and surveys of, behavior and mental health problems were the subject of several presentations, while exercise problems were highlighted in others. The scientific conference, since its inception, has been the keynote day of the national meeting for PWS families. This allows not only a dialog among researchers, but also a dialog between those doing research at the most basic level and the parents. This latter exchange often sparks a whole chain of research ideas and provides investigators with a clear link to the outcome of often solitary work. 1. ANALYSIS OF PARENT-OF-ORIGIN SPECIFIC DNA METHYLATION AT SNRPN, AND PW71 IN TISSUES: IMPLICATION FOR PRENATAL DIAGNOSIS. Kubota T1, Aradhya S1, Macha M1, Smith, ACM1, Surh LC2, Satish J3, Verp MS4, Johnson A5, Christian SL1, Ledbetter DH1. 1Diagnostic Development Branch, National Center for Human Genome Research, NIH, Bethesda, MD, 2Children’s Hospital of Eastern Ontario, Canada; 3Sinai Hospital of Baltimore, MD; 4University of Chicago, IL; 5Prenatal Diagnostic Center, MA. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental disorders caused by absence of paternal or maternal contributions of the chromosome region 15q11–q13, resulting from deletions, uniparental disomy (UPD), or rare imprinting mutations. Molecular cytogenetic diagnosis is currently performed using a combination of fluorescence in situ hybridization (FISH), DNA polymorphism analysis, and DNA methylation analysis. Only methylation analysis will detect all three categories of PWS abnormalities, but its reliability in tissues other than peripheral blood has not been examined extensively. Therefore, we examined the methylation status at the CpG island of the small nuclear ribonucleoprotein-associated polypeptide (SNRPN) gene and at the PW71 locus using normal and abnormal lymphoblast (LB) cell lines (n 4 48), amniotic fluid (AF) cell cultures (n 4 25), cultured chorionic villus samples (CVS, n 4 17), and fetal tissues (n 4 18) by Southern blot analysis with methylation-sensitive enzymes. Of these samples, 20 LB cell lines, 3 AF cultures, 1 CVS, and 15 fetal tissues had been diagnosed previously as having deletions or UPD by other molecular methods. Methylation status at SNRPN showed consistent results when compared with FISH or DNA polymorphism analysis using all cell types tested. However, the methylation pattern for PW71 was inconsistent when compared with other tests and should not be used on tissues other than peripheral blood. Therefore, we conclude that SNRPN, but not PW71 methylation analysis, may be useful for diagnosis of PWS/ AS on LB cell lines, cultured AF, or CVS and will allow, for the first time, prenatal diagnosis for families known to carry imprinting center defects.