Wijmenga C, Padberg G W, Moerer P, Wiegant J, Liem L, Brouwer O F, Milner E C, Weber J L, van Ommen G B, Sandkuyl L A
Department of Neurology, Leiden University, The Netherlands.
Genomics. 1991 Apr;9(4):570-5. doi: 10.1016/0888-7543(91)90348-i.
We have recently assigned the facioscapulohumeral muscular dystrophy (FSHD) gene to chromome 4 by linkage to the microsatellite marker Mfd 22 (locus D4S171). We now report that D4S139, a VNTR locus, is much more closely linked to FSHD. Two-point linkage analysis between FSHD and D4S139 in nine informative families showed a maximum combined lod score (Zmax) of 17.28 at a recombination fraction theta of 0.027. Multipoint linkage analysis between FSHD and the loci D4S139 and D4S171 resulted in a peak lod score of 20.21 at 2.7 cM from D4S139. Due to the small number of recombinants found with D4S139, the position of the FSHD gene relative to that of D4S139 could not be established with certainty. D4S139 was mapped to chromosome 4q35-qter by in situ hybridization, thus firmly establishing the location of the FSHD gene in the subtelomeric region of chromosome 4q. One small family yielded a negative lod score for D4S139. In the other families no significant evidence for genetic heterogeneity was obtained. Studies of additional markers and new families will improve the map of the FSHD region, reveal possible genetic heterogeneity, and allow better diagnostic reliability.
我们最近通过与微卫星标记Mfd 22（基因座D4S171）的连锁分析，将面肩肱型肌营养不良症（FSHD）基因定位于4号染色体。我们现在报告，一个可变数目串联重复序列（VNTR）基因座D4S139与FSHD的连锁更为紧密。在9个信息充分的家系中对FSHD和D4S139进行两点连锁分析，结果显示在重组率θ为0.027时，最大合并对数优势分数（Zmax）为17.28。对FSHD与基因座D4S139和D4S171进行多点连锁分析，结果在距D4S139 2.7厘摩（cM）处得到峰值对数优势分数20.21。由于与D4S139发现的重组体数量较少，无法确定FSHD基因相对于D4S139的位置。通过原位杂交将D4S139定位于4号染色体的4q35 - qter，从而确定了FSHD基因在4号染色体q臂亚端粒区域的位置。一个小家系对D4S139得出负对数优势分数。在其他家系中未获得遗传异质性的显著证据。对更多标记和新的家系进行研究将改善FSHD区域的图谱，揭示可能存在的遗传异质性，并提高诊断的可靠性。
