Kupke K G, Graeber M B, Müller U
Division of Genetics, Children's Hospital, Boston, MA 02115.
Am J Hum Genet. 1992 Apr;50(4):808-15.
The study of rare genetic forms of dystonia and parkinsonism permits positional cloning of genes potentially involved in more common, multifactorial forms of these diseases. One movement disorder amenable to molecular genetic analysis is the X-linked dystonia-parkinsonism syndrome (XDP). This disease is endemic to the Philippines where it originated by a genetic founder effect. Linkage analysis was performed with DNA from 14 XDP kindreds by using 12 polymorphic DNA sequences in Xp11-Xq22. Two-point analysis demonstrated maximum lod scores of 5.45, 4.95, 4.28, and 5.99 for DXS106, DXS159, PGK1, and DXS72, respectively, at recombination fractions of zero (DXS106 and DXS159), .01 (PGK1), and .04 (DXS72). Multipoint analysis resulted in a maximum-likelihood score (Zmax) of 8.41 with a (Zmax - 1) support interval of 9 cM between DXS159 and DXS72 (Xq12-q21.1). In 19 XDP kindreds significant linkage disequilibrium was found for loci DXS72 (delta = .47), PGK1 (delta = .36), DXS95 (delta = .30), DXS106 (delta = .28), and DXS159 (delta = .26). These data indicate that the gene mutated in XDP (locus DYT3) is located in Xq12-q21.1.
对肌张力障碍和帕金森症的罕见遗传形式进行研究，有助于对可能涉及这些疾病更常见的多因素形式的基因进行定位克隆。一种适合分子遗传学分析的运动障碍是X连锁肌张力障碍-帕金森综合征（XDP）。这种疾病在菲律宾流行，它起源于遗传奠基者效应。利用Xp11 - Xq22区域的12个多态性DNA序列，对14个XDP家族的DNA进行连锁分析。两点分析表明，在重组率为零（DXS106和DXS159）、0.01（PGK1）和0.04（DXS72）时，DXS106、DXS159、PGK1和DXS72的最大lod分数分别为5.45、4.95、4.28和5.99。多点分析得出最大似然分数（Zmax）为8.41，在DXS159和DXS72（Xq12 - q21.1）之间（Zmax - 1）支持区间为9 cM。在19个XDP家族中，发现DXS72（δ = 0.47）、PGK1（δ = 0.36）、DXS95（δ = 0.30）、DXS106（δ = 0.28）和DXS159（δ = 0.26）位点存在显著的连锁不平衡。这些数据表明，XDP中发生突变的基因（位点DYT3）位于Xq12 - q21.1。
