Runte Maren, Varon Raymonda, Horn Denise, Horsthemke Bernhard, Buiting Karin
Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Hum Genet. 2005 Feb;116(3):228-30. doi: 10.1007/s00439-004-1219-2. Epub 2004 Nov 23.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurogenetic disorders caused by the loss of function of imprinted genes in 15q11-q13. The maternally expressed UBE3A gene is affected in AS. Four protein-encoding genes (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438A, HBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear. To examine the role of the HBII-52 snoRNA genes, we have reinvestigated an AS family with a submicroscopic deletion spanning UBE3A and flanking sequences. By fine mapping of the centromeric deletion breakpoint in this family, we have found that the deletion affects all of the 47 HBII-52 genes. Since the complete loss of the HBII-52 genes in family members who carry the deletion on their paternal chromosome is not associated with an obvious clinical phenotype, we conclude that HBII-52 snoRNA genes do not play a major role in PWS. However, we cannot exclude the possibility that the loss of HBII-52 has a phenotypic effect when accompanied by the loss of function of other genes in 15q11-q13.
普拉德-威利综合征（PWS）和安吉尔曼综合征（AS）是由15q11-q13印记基因功能丧失引起的两种不同的神经遗传疾病。母源表达的UBE3A基因在AS中受到影响。四个蛋白质编码基因（MKRN3、MAGEL2、NDN和SNURF-SNRPN）以及几个小核仁（sno）RNA基因（HBII-13、HBII-436、HBII-85、HBII-438A、HBII-438B和HBII-52）仅从父源染色体表达，但其对PWS的作用尚不清楚。为了研究HBII-52 snoRNA基因的作用，我们重新研究了一个患有亚显微缺失的AS家族，该缺失跨越UBE3A及其侧翼序列。通过对该家族着丝粒缺失断点的精细定位，我们发现该缺失影响了所有47个HBII-52基因。由于在父源染色体上携带该缺失的家族成员中HBII-52基因的完全缺失与明显的临床表型无关，我们得出结论，HBII-52 snoRNA基因在PWS中不发挥主要作用。然而，我们不能排除当HBII-52缺失与15q11-q13中其他基因功能丧失同时发生时具有表型效应的可能性。
