Gustavsson P, Garelli E, Draptchinskaia N, Ball S, Willig T N, Tentler D, Dianzani I, Punnett H H, Shafer F E, Cario H, Ramenghi U, Glomstein A, Pfeiffer R A, Goringe A, Olivieri N F, Smibert E, Tchernia G, Elinder G, Dahl N
Unit of Clinical Genetics, Department of Genetics and Pathology, Uppsala University Children's Hospital, Uppsala, Sweden.
Am J Hum Genet. 1998 Nov;63(5):1388-95. doi: 10.1086/302100.
Diamond-Blackfan anemia (DBA) is a rare pure red-cell hypoplasia of unknown etiology and pathogenesis. A major DBA locus has previously been localized to chromosome 19q13.2. Samples from additional families have been collected to identify key recombinations, microdeletions, and the possibility of heterogeneity for the disorder. In total, 29 multiplex DBA families and 50 families that comprise sporadic DBA cases have been analyzed with polymorphic 19q13 markers, including a newly identified short-tandem repeat in the critical gene region. The results from DNA analysis of 29 multiplex families revealed that 26 of these were consistent with a DBA gene on 19q localized to within a 4.1-cM interval restricted by loci D19S200 and D19S178; however, in three multiplex families, the DBA candidate region on 19q13 was excluded from the segregation of marker alleles. Our results suggest genetic heterogeneity for DBA, and we show that a gene region on chromosome 19q segregates with the disease in the majority of familial cases. Among the 50 families comprising sporadic DBA cases, we identified two novel and overlapping microdeletions on chromosome 19q13. In combination, the three known microdeletions associated with DBA restrict the critical gene region to approximately 1 Mb. The results indicate that a proportion of sporadic DBA cases are caused by deletions in the 19q13 region.
钻石黑范贫血（DBA）是一种病因和发病机制不明的罕见纯红细胞再生障碍。此前已将一个主要的DBA基因座定位到19号染色体q13.2区域。已收集了更多家族的样本，以确定关键重组、微缺失以及该疾病的异质性可能性。总共对29个多位点DBA家族和50个包含散发性DBA病例的家族进行了19q13多态性标记分析，包括在关键基因区域新发现的短串联重复序列。对29个多位点家族的DNA分析结果显示，其中26个家族与位于由D19S200和D19S178位点限定的4.1厘摩区间内的19q上的DBA基因一致；然而，在三个多位点家族中，19q13上的DBA候选区域被排除在标记等位基因的分离之外。我们的结果提示DBA存在遗传异质性，并且我们表明在大多数家族性病例中，19号染色体q上的一个基因区域与该疾病共分离。在50个包含散发性DBA病例的家族中，我们在19q13染色体上鉴定出两个新的且重叠的微缺失。与DBA相关的三个已知微缺失合起来将关键基因区域限制在约1兆碱基。结果表明，一部分散发性DBA病例是由19q13区域的缺失引起的。
