Reilly D S, Lewis R A, Ledbetter D H, Nussbaum R L
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104.
Am J Hum Genet. 1988 May;42(5):748-55.
The Lowe oculocerebrorenal syndrome (OCRL) is characterized by congenital cataract, mental retardation, and defective renal tubular function. A map assignment of OCRL to Xq24-q26 has been made previously by linkage analysis with DXS42 at Xq24-q26 (theta = 0, z = 5.09) and with DXS10 at Xq26 (theta = 0, z = 6.45). Two additional families were studied and three additional polymorphisms were identified at DXS42 by using a 35-kb sequence isolated with the probe detecting the original polymorphism at DXS42. With additional OCRL families made informative for DXS42, theta remained 0 with z = 6.63; and for DXS10 theta = 0.03 and z = 7.07. Evidence for placing OCRL at Xq25 also comes from a female with Lowe syndrome and an X;3 translocation. We have used the Xq25 breakpoint in this patient to determine the position of OCRL relative to the two linked markers. Each derivative chromosome was isolated away from its normal counterpart in somatic cell hybrids. DXS42 was mapped to the derivative chromosome X containing Xpterq25, and DXS10 was mapped to the derivative chromosome 3 containing Xq25-qter. The markers DXS10 and DXS42 therefore show tight linkage with OCRL in six families and flank the Xq25 breakpoint in a female patient with an X;3 translocation. Linkage analysis with flanking markers was used to assess OCRL carrier status in women at risk. Results, when compared with carrier determination by ophthalmologic examination, indicated that the slit-lamp exam can be a sensitive and specific method of carrier determination in many cases.
洛氏眼脑肾综合征（OCRL）的特征为先天性白内障、智力发育迟缓以及肾小管功能缺陷。先前通过与位于Xq24 - q26的DXS42（θ = 0，z = 5.09）以及位于Xq26的DXS10（θ = 0，z = 6.45）进行连锁分析，已将OCRL定位于Xq24 - q26。研究了另外两个家系，并通过使用与检测DXS42原始多态性的探针分离出的35 kb序列，在DXS42处鉴定出另外三个多态性。对于更多使DXS42具有信息性的OCRL家系，θ仍为0，z = 6.63；对于DXS10，θ = 0.03，z = 7.07。将OCRL定位于Xq25的证据还来自一名患有洛氏综合征且有X;3易位的女性。我们利用该患者的Xq25断点来确定OCRL相对于两个连锁标记的位置。在体细胞杂种中，将每个衍生染色体与其正常对应物分离。DXS42定位于包含Xpterq25的衍生X染色体上，DXS10定位于包含Xq25 - qter的衍生3号染色体上。因此，标记DXS10和DXS42在六个家系中显示与OCRL紧密连锁，并且在一名患有X;3易位的女性患者中位于Xq25断点两侧。使用侧翼标记进行连锁分析以评估有风险女性的OCRL携带者状态。与通过眼科检查确定携带者的结果相比，结果表明在许多情况下，裂隙灯检查可能是一种敏感且特异的携带者确定方法。
